ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5251C>T (p.Arg1751Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Apr 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5251C>T (p.Arg1751Ter)
Variation ID: 55480 Accession: VCV000055480.84
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43057078 (GRCh38) [ NCBI UCSC ] 17: 41209095 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 3, 2015 Oct 20, 2024 Apr 22, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5251C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Arg1751Ter nonsense NM_001407571.1:c.5038C>T NP_001394500.1:p.Arg1680Ter nonsense NM_001407581.1:c.5317C>T NP_001394510.1:p.Arg1773Ter nonsense NM_001407582.1:c.5317C>T NP_001394511.1:p.Arg1773Ter nonsense NM_001407583.1:c.5314C>T NP_001394512.1:p.Arg1772Ter nonsense NM_001407585.1:c.5314C>T NP_001394514.1:p.Arg1772Ter nonsense NM_001407587.1:c.5314C>T NP_001394516.1:p.Arg1772Ter nonsense NM_001407590.1:c.5311C>T NP_001394519.1:p.Arg1771Ter nonsense NM_001407591.1:c.5311C>T NP_001394520.1:p.Arg1771Ter nonsense NM_001407593.1:c.5251C>T NP_001394522.1:p.Arg1751Ter nonsense NM_001407594.1:c.5251C>T NP_001394523.1:p.Arg1751Ter nonsense NM_001407596.1:c.5251C>T NP_001394525.1:p.Arg1751Ter nonsense NM_001407597.1:c.5251C>T NP_001394526.1:p.Arg1751Ter nonsense NM_001407598.1:c.5251C>T NP_001394527.1:p.Arg1751Ter nonsense NM_001407602.1:c.5251C>T NP_001394531.1:p.Arg1751Ter nonsense NM_001407603.1:c.5251C>T NP_001394532.1:p.Arg1751Ter nonsense NM_001407605.1:c.5251C>T NP_001394534.1:p.Arg1751Ter nonsense NM_001407610.1:c.5248C>T NP_001394539.1:p.Arg1750Ter nonsense NM_001407611.1:c.5248C>T NP_001394540.1:p.Arg1750Ter nonsense NM_001407612.1:c.5248C>T NP_001394541.1:p.Arg1750Ter nonsense NM_001407613.1:c.5248C>T NP_001394542.1:p.Arg1750Ter nonsense NM_001407614.1:c.5248C>T NP_001394543.1:p.Arg1750Ter nonsense NM_001407615.1:c.5248C>T NP_001394544.1:p.Arg1750Ter nonsense NM_001407616.1:c.5248C>T NP_001394545.1:p.Arg1750Ter nonsense NM_001407617.1:c.5248C>T NP_001394546.1:p.Arg1750Ter nonsense NM_001407618.1:c.5248C>T NP_001394547.1:p.Arg1750Ter nonsense NM_001407619.1:c.5248C>T NP_001394548.1:p.Arg1750Ter nonsense NM_001407620.1:c.5248C>T NP_001394549.1:p.Arg1750Ter nonsense NM_001407621.1:c.5248C>T NP_001394550.1:p.Arg1750Ter nonsense NM_001407622.1:c.5248C>T NP_001394551.1:p.Arg1750Ter nonsense NM_001407623.1:c.5248C>T NP_001394552.1:p.Arg1750Ter nonsense NM_001407624.1:c.5248C>T NP_001394553.1:p.Arg1750Ter nonsense NM_001407625.1:c.5248C>T NP_001394554.1:p.Arg1750Ter nonsense NM_001407626.1:c.5248C>T NP_001394555.1:p.Arg1750Ter nonsense NM_001407627.1:c.5245C>T NP_001394556.1:p.Arg1749Ter nonsense NM_001407628.1:c.5245C>T NP_001394557.1:p.Arg1749Ter nonsense NM_001407629.1:c.5245C>T NP_001394558.1:p.Arg1749Ter nonsense NM_001407630.1:c.5245C>T NP_001394559.1:p.Arg1749Ter nonsense NM_001407631.1:c.5245C>T NP_001394560.1:p.Arg1749Ter nonsense NM_001407632.1:c.5245C>T NP_001394561.1:p.Arg1749Ter nonsense NM_001407633.1:c.5245C>T NP_001394562.1:p.Arg1749Ter nonsense NM_001407634.1:c.5245C>T NP_001394563.1:p.Arg1749Ter nonsense NM_001407635.1:c.5245C>T NP_001394564.1:p.Arg1749Ter nonsense NM_001407636.1:c.5245C>T NP_001394565.1:p.Arg1749Ter nonsense NM_001407637.1:c.5245C>T NP_001394566.1:p.Arg1749Ter nonsense NM_001407638.1:c.5245C>T NP_001394567.1:p.Arg1749Ter nonsense NM_001407639.1:c.5245C>T NP_001394568.1:p.Arg1749Ter nonsense NM_001407640.1:c.5245C>T NP_001394569.1:p.Arg1749Ter nonsense NM_001407641.1:c.5245C>T NP_001394570.1:p.Arg1749Ter nonsense NM_001407642.1:c.5245C>T NP_001394571.1:p.Arg1749Ter nonsense NM_001407644.1:c.5242C>T NP_001394573.1:p.Arg1748Ter nonsense NM_001407645.1:c.5242C>T NP_001394574.1:p.Arg1748Ter nonsense NM_001407646.1:c.5239C>T NP_001394575.1:p.Arg1747Ter nonsense NM_001407647.1:c.5236C>T NP_001394576.1:p.Arg1746Ter nonsense NM_001407648.1:c.5194C>T NP_001394577.1:p.Arg1732Ter nonsense NM_001407649.1:c.5191C>T NP_001394578.1:p.Arg1731Ter nonsense NM_001407652.1:c.5173C>T NP_001394581.1:p.Arg1725Ter nonsense NM_001407653.1:c.5173C>T NP_001394582.1:p.Arg1725Ter nonsense NM_001407654.1:c.5173C>T NP_001394583.1:p.Arg1725Ter nonsense NM_001407655.1:c.5173C>T NP_001394584.1:p.Arg1725Ter nonsense NM_001407656.1:c.5170C>T NP_001394585.1:p.Arg1724Ter nonsense NM_001407657.1:c.5170C>T NP_001394586.1:p.Arg1724Ter nonsense NM_001407658.1:c.5170C>T NP_001394587.1:p.Arg1724Ter nonsense NM_001407659.1:c.5167C>T NP_001394588.1:p.Arg1723Ter nonsense NM_001407660.1:c.5167C>T NP_001394589.1:p.Arg1723Ter nonsense NM_001407661.1:c.5167C>T NP_001394590.1:p.Arg1723Ter nonsense NM_001407662.1:c.5167C>T NP_001394591.1:p.Arg1723Ter nonsense NM_001407663.1:c.5167C>T NP_001394592.1:p.Arg1723Ter nonsense NM_001407664.1:c.5128C>T NP_001394593.1:p.Arg1710Ter nonsense NM_001407665.1:c.5128C>T NP_001394594.1:p.Arg1710Ter nonsense NM_001407666.1:c.5128C>T NP_001394595.1:p.Arg1710Ter nonsense NM_001407667.1:c.5128C>T NP_001394596.1:p.Arg1710Ter nonsense NM_001407668.1:c.5128C>T NP_001394597.1:p.Arg1710Ter nonsense NM_001407669.1:c.5128C>T NP_001394598.1:p.Arg1710Ter nonsense NM_001407670.1:c.5125C>T NP_001394599.1:p.Arg1709Ter nonsense NM_001407671.1:c.5125C>T NP_001394600.1:p.Arg1709Ter nonsense NM_001407672.1:c.5125C>T NP_001394601.1:p.Arg1709Ter nonsense NM_001407673.1:c.5125C>T NP_001394602.1:p.Arg1709Ter nonsense NM_001407674.1:c.5125C>T NP_001394603.1:p.Arg1709Ter nonsense NM_001407675.1:c.5125C>T NP_001394604.1:p.Arg1709Ter nonsense NM_001407676.1:c.5125C>T NP_001394605.1:p.Arg1709Ter nonsense NM_001407677.1:c.5125C>T NP_001394606.1:p.Arg1709Ter nonsense NM_001407678.1:c.5125C>T NP_001394607.1:p.Arg1709Ter nonsense NM_001407679.1:c.5125C>T NP_001394608.1:p.Arg1709Ter nonsense NM_001407680.1:c.5125C>T NP_001394609.1:p.Arg1709Ter nonsense NM_001407681.1:c.5122C>T NP_001394610.1:p.Arg1708Ter nonsense NM_001407682.1:c.5122C>T NP_001394611.1:p.Arg1708Ter nonsense NM_001407683.1:c.5122C>T NP_001394612.1:p.Arg1708Ter nonsense NM_001407684.1:c.5251C>T NP_001394613.1:p.Arg1751Ter nonsense NM_001407685.1:c.5122C>T NP_001394614.1:p.Arg1708Ter nonsense NM_001407686.1:c.5122C>T NP_001394615.1:p.Arg1708Ter nonsense NM_001407687.1:c.5122C>T NP_001394616.1:p.Arg1708Ter nonsense NM_001407688.1:c.5122C>T NP_001394617.1:p.Arg1708Ter nonsense NM_001407689.1:c.5122C>T NP_001394618.1:p.Arg1708Ter nonsense NM_001407690.1:c.5119C>T NP_001394619.1:p.Arg1707Ter nonsense NM_001407691.1:c.5119C>T NP_001394620.1:p.Arg1707Ter nonsense NM_001407692.1:c.5110C>T NP_001394621.1:p.Arg1704Ter nonsense NM_001407694.1:c.5110C>T NP_001394623.1:p.Arg1704Ter nonsense NM_001407695.1:c.5110C>T NP_001394624.1:p.Arg1704Ter nonsense NM_001407696.1:c.5110C>T NP_001394625.1:p.Arg1704Ter nonsense NM_001407697.1:c.5110C>T NP_001394626.1:p.Arg1704Ter nonsense NM_001407698.1:c.5110C>T NP_001394627.1:p.Arg1704Ter nonsense NM_001407724.1:c.5110C>T NP_001394653.1:p.Arg1704Ter nonsense NM_001407725.1:c.5110C>T NP_001394654.1:p.Arg1704Ter nonsense NM_001407726.1:c.5110C>T NP_001394655.1:p.Arg1704Ter nonsense NM_001407727.1:c.5110C>T NP_001394656.1:p.Arg1704Ter nonsense NM_001407728.1:c.5110C>T NP_001394657.1:p.Arg1704Ter nonsense NM_001407729.1:c.5110C>T NP_001394658.1:p.Arg1704Ter nonsense NM_001407730.1:c.5110C>T NP_001394659.1:p.Arg1704Ter nonsense NM_001407731.1:c.5110C>T NP_001394660.1:p.Arg1704Ter nonsense NM_001407732.1:c.5107C>T NP_001394661.1:p.Arg1703Ter nonsense NM_001407733.1:c.5107C>T NP_001394662.1:p.Arg1703Ter nonsense NM_001407734.1:c.5107C>T NP_001394663.1:p.Arg1703Ter nonsense NM_001407735.1:c.5107C>T NP_001394664.1:p.Arg1703Ter nonsense NM_001407736.1:c.5107C>T NP_001394665.1:p.Arg1703Ter nonsense NM_001407737.1:c.5107C>T NP_001394666.1:p.Arg1703Ter nonsense NM_001407738.1:c.5107C>T NP_001394667.1:p.Arg1703Ter nonsense NM_001407739.1:c.5107C>T NP_001394668.1:p.Arg1703Ter nonsense NM_001407740.1:c.5107C>T NP_001394669.1:p.Arg1703Ter nonsense NM_001407741.1:c.5107C>T NP_001394670.1:p.Arg1703Ter nonsense NM_001407742.1:c.5107C>T NP_001394671.1:p.Arg1703Ter nonsense NM_001407743.1:c.5107C>T NP_001394672.1:p.Arg1703Ter nonsense NM_001407744.1:c.5107C>T NP_001394673.1:p.Arg1703Ter nonsense NM_001407745.1:c.5107C>T NP_001394674.1:p.Arg1703Ter nonsense NM_001407746.1:c.5107C>T NP_001394675.1:p.Arg1703Ter nonsense NM_001407747.1:c.5107C>T NP_001394676.1:p.Arg1703Ter nonsense NM_001407748.1:c.5107C>T NP_001394677.1:p.Arg1703Ter nonsense NM_001407749.1:c.5107C>T NP_001394678.1:p.Arg1703Ter nonsense NM_001407750.1:c.5107C>T NP_001394679.1:p.Arg1703Ter nonsense NM_001407751.1:c.5107C>T NP_001394680.1:p.Arg1703Ter nonsense NM_001407752.1:c.5107C>T NP_001394681.1:p.Arg1703Ter nonsense NM_001407838.1:c.5104C>T NP_001394767.1:p.Arg1702Ter nonsense NM_001407839.1:c.5104C>T NP_001394768.1:p.Arg1702Ter nonsense NM_001407841.1:c.5104C>T NP_001394770.1:p.Arg1702Ter nonsense NM_001407842.1:c.5104C>T NP_001394771.1:p.Arg1702Ter nonsense NM_001407843.1:c.5104C>T NP_001394772.1:p.Arg1702Ter nonsense NM_001407844.1:c.5104C>T NP_001394773.1:p.Arg1702Ter nonsense NM_001407845.1:c.5104C>T NP_001394774.1:p.Arg1702Ter nonsense NM_001407846.1:c.5104C>T NP_001394775.1:p.Arg1702Ter nonsense NM_001407847.1:c.5104C>T NP_001394776.1:p.Arg1702Ter nonsense NM_001407848.1:c.5104C>T NP_001394777.1:p.Arg1702Ter nonsense NM_001407849.1:c.5104C>T NP_001394778.1:p.Arg1702Ter nonsense NM_001407850.1:c.5104C>T NP_001394779.1:p.Arg1702Ter nonsense NM_001407851.1:c.5104C>T NP_001394780.1:p.Arg1702Ter nonsense NM_001407852.1:c.5104C>T NP_001394781.1:p.Arg1702Ter nonsense NM_001407853.1:c.5104C>T NP_001394782.1:p.Arg1702Ter nonsense NM_001407854.1:c.5251C>T NP_001394783.1:p.Arg1751Ter nonsense NM_001407858.1:c.5248C>T NP_001394787.1:p.Arg1750Ter nonsense NM_001407859.1:c.5248C>T NP_001394788.1:p.Arg1750Ter nonsense NM_001407860.1:c.5248C>T NP_001394789.1:p.Arg1750Ter nonsense NM_001407861.1:c.5245C>T NP_001394790.1:p.Arg1749Ter nonsense NM_001407862.1:c.5050C>T NP_001394791.1:p.Arg1684Ter nonsense NM_001407863.1:c.5047C>T NP_001394792.1:p.Arg1683Ter nonsense NM_001407874.1:c.5044C>T NP_001394803.1:p.Arg1682Ter nonsense NM_001407875.1:c.5044C>T NP_001394804.1:p.Arg1682Ter nonsense NM_001407879.1:c.5041C>T NP_001394808.1:p.Arg1681Ter nonsense NM_001407881.1:c.5041C>T NP_001394810.1:p.Arg1681Ter nonsense NM_001407882.1:c.5041C>T NP_001394811.1:p.Arg1681Ter nonsense NM_001407884.1:c.5041C>T NP_001394813.1:p.Arg1681Ter nonsense NM_001407885.1:c.5041C>T NP_001394814.1:p.Arg1681Ter nonsense NM_001407886.1:c.5041C>T NP_001394815.1:p.Arg1681Ter nonsense NM_001407887.1:c.5041C>T NP_001394816.1:p.Arg1681Ter nonsense NM_001407889.1:c.5041C>T NP_001394818.1:p.Arg1681Ter nonsense NM_001407894.1:c.5038C>T NP_001394823.1:p.Arg1680Ter nonsense NM_001407895.1:c.5038C>T NP_001394824.1:p.Arg1680Ter nonsense NM_001407896.1:c.5038C>T NP_001394825.1:p.Arg1680Ter nonsense NM_001407897.1:c.5038C>T NP_001394826.1:p.Arg1680Ter nonsense NM_001407898.1:c.5038C>T NP_001394827.1:p.Arg1680Ter nonsense NM_001407899.1:c.5038C>T NP_001394828.1:p.Arg1680Ter nonsense NM_001407900.1:c.5038C>T NP_001394829.1:p.Arg1680Ter nonsense NM_001407902.1:c.5038C>T NP_001394831.1:p.Arg1680Ter nonsense NM_001407904.1:c.5038C>T NP_001394833.1:p.Arg1680Ter nonsense NM_001407906.1:c.5038C>T NP_001394835.1:p.Arg1680Ter nonsense NM_001407907.1:c.5038C>T NP_001394836.1:p.Arg1680Ter nonsense NM_001407908.1:c.5038C>T NP_001394837.1:p.Arg1680Ter nonsense NM_001407909.1:c.5038C>T NP_001394838.1:p.Arg1680Ter nonsense NM_001407910.1:c.5038C>T NP_001394839.1:p.Arg1680Ter nonsense NM_001407915.1:c.5035C>T NP_001394844.1:p.Arg1679Ter nonsense NM_001407916.1:c.5035C>T NP_001394845.1:p.Arg1679Ter nonsense NM_001407917.1:c.5035C>T NP_001394846.1:p.Arg1679Ter nonsense NM_001407918.1:c.5035C>T NP_001394847.1:p.Arg1679Ter nonsense NM_001407919.1:c.5128C>T NP_001394848.1:p.Arg1710Ter nonsense NM_001407920.1:c.4987C>T NP_001394849.1:p.Arg1663Ter nonsense NM_001407921.1:c.4987C>T NP_001394850.1:p.Arg1663Ter nonsense NM_001407922.1:c.4987C>T NP_001394851.1:p.Arg1663Ter nonsense NM_001407923.1:c.4987C>T NP_001394852.1:p.Arg1663Ter nonsense NM_001407924.1:c.4987C>T NP_001394853.1:p.Arg1663Ter nonsense NM_001407925.1:c.4987C>T NP_001394854.1:p.Arg1663Ter nonsense NM_001407926.1:c.4987C>T NP_001394855.1:p.Arg1663Ter nonsense NM_001407927.1:c.4984C>T NP_001394856.1:p.Arg1662Ter nonsense NM_001407928.1:c.4984C>T NP_001394857.1:p.Arg1662Ter nonsense NM_001407929.1:c.4984C>T NP_001394858.1:p.Arg1662Ter nonsense NM_001407930.1:c.4984C>T NP_001394859.1:p.Arg1662Ter nonsense NM_001407931.1:c.4984C>T NP_001394860.1:p.Arg1662Ter nonsense NM_001407932.1:c.4984C>T NP_001394861.1:p.Arg1662Ter nonsense NM_001407933.1:c.4984C>T NP_001394862.1:p.Arg1662Ter nonsense NM_001407934.1:c.4981C>T NP_001394863.1:p.Arg1661Ter nonsense NM_001407935.1:c.4981C>T NP_001394864.1:p.Arg1661Ter nonsense NM_001407936.1:c.4981C>T NP_001394865.1:p.Arg1661Ter nonsense NM_001407937.1:c.5128C>T NP_001394866.1:p.Arg1710Ter nonsense NM_001407938.1:c.5128C>T NP_001394867.1:p.Arg1710Ter nonsense NM_001407939.1:c.5125C>T NP_001394868.1:p.Arg1709Ter nonsense NM_001407940.1:c.5125C>T NP_001394869.1:p.Arg1709Ter nonsense NM_001407941.1:c.5122C>T NP_001394870.1:p.Arg1708Ter nonsense NM_001407942.1:c.5110C>T NP_001394871.1:p.Arg1704Ter nonsense NM_001407943.1:c.5107C>T NP_001394872.1:p.Arg1703Ter nonsense NM_001407944.1:c.5107C>T NP_001394873.1:p.Arg1703Ter nonsense NM_001407945.1:c.5107C>T NP_001394874.1:p.Arg1703Ter nonsense NM_001407946.1:c.4918C>T NP_001394875.1:p.Arg1640Ter nonsense NM_001407947.1:c.4918C>T NP_001394876.1:p.Arg1640Ter nonsense NM_001407948.1:c.4918C>T NP_001394877.1:p.Arg1640Ter nonsense NM_001407949.1:c.4918C>T NP_001394878.1:p.Arg1640Ter nonsense NM_001407950.1:c.4915C>T NP_001394879.1:p.Arg1639Ter nonsense NM_001407951.1:c.4915C>T NP_001394880.1:p.Arg1639Ter nonsense NM_001407952.1:c.4915C>T NP_001394881.1:p.Arg1639Ter nonsense NM_001407953.1:c.4915C>T NP_001394882.1:p.Arg1639Ter nonsense NM_001407954.1:c.4915C>T NP_001394883.1:p.Arg1639Ter nonsense NM_001407955.1:c.4915C>T NP_001394884.1:p.Arg1639Ter nonsense NM_001407956.1:c.4912C>T NP_001394885.1:p.Arg1638Ter nonsense NM_001407957.1:c.4912C>T NP_001394886.1:p.Arg1638Ter nonsense NM_001407958.1:c.4912C>T NP_001394887.1:p.Arg1638Ter nonsense NM_001407959.1:c.4870C>T NP_001394888.1:p.Arg1624Ter nonsense NM_001407960.1:c.4867C>T NP_001394889.1:p.Arg1623Ter nonsense NM_001407962.1:c.4867C>T NP_001394891.1:p.Arg1623Ter nonsense NM_001407963.1:c.4864C>T NP_001394892.1:p.Arg1622Ter nonsense NM_001407964.1:c.4789C>T NP_001394893.1:p.Arg1597Ter nonsense NM_001407965.1:c.4744C>T NP_001394894.1:p.Arg1582Ter nonsense NM_001407966.1:c.4363C>T NP_001394895.1:p.Arg1455Ter nonsense NM_001407967.1:c.4360C>T NP_001394896.1:p.Arg1454Ter nonsense NM_001407968.1:c.2647C>T NP_001394897.1:p.Arg883Ter nonsense NM_001407969.1:c.2644C>T NP_001394898.1:p.Arg882Ter nonsense NM_001407970.1:c.2008C>T NP_001394899.1:p.Arg670Ter nonsense NM_001407971.1:c.2008C>T NP_001394900.1:p.Arg670Ter nonsense NM_001407972.1:c.2005C>T NP_001394901.1:p.Arg669Ter nonsense NM_001407973.1:c.1942C>T NP_001394902.1:p.Arg648Ter nonsense NM_001407974.1:c.1942C>T NP_001394903.1:p.Arg648Ter nonsense NM_001407975.1:c.1942C>T NP_001394904.1:p.Arg648Ter nonsense NM_001407976.1:c.1942C>T NP_001394905.1:p.Arg648Ter nonsense NM_001407977.1:c.1942C>T NP_001394906.1:p.Arg648Ter nonsense NM_001407978.1:c.1942C>T NP_001394907.1:p.Arg648Ter nonsense NM_001407979.1:c.1939C>T NP_001394908.1:p.Arg647Ter nonsense NM_001407980.1:c.1939C>T NP_001394909.1:p.Arg647Ter nonsense NM_001407981.1:c.1939C>T NP_001394910.1:p.Arg647Ter nonsense NM_001407982.1:c.1939C>T NP_001394911.1:p.Arg647Ter nonsense NM_001407983.1:c.1939C>T NP_001394912.1:p.Arg647Ter nonsense NM_001407984.1:c.1939C>T NP_001394913.1:p.Arg647Ter nonsense NM_001407985.1:c.1939C>T NP_001394914.1:p.Arg647Ter nonsense NM_001407986.1:c.1939C>T NP_001394915.1:p.Arg647Ter nonsense NM_001407990.1:c.1939C>T NP_001394919.1:p.Arg647Ter nonsense NM_001407991.1:c.1939C>T NP_001394920.1:p.Arg647Ter nonsense NM_001407992.1:c.1939C>T NP_001394921.1:p.Arg647Ter nonsense NM_001407993.1:c.1939C>T NP_001394922.1:p.Arg647Ter nonsense NM_001408392.1:c.1936C>T NP_001395321.1:p.Arg646Ter nonsense NM_001408396.1:c.1936C>T NP_001395325.1:p.Arg646Ter nonsense NM_001408397.1:c.1936C>T NP_001395326.1:p.Arg646Ter nonsense NM_001408398.1:c.1936C>T NP_001395327.1:p.Arg646Ter nonsense NM_001408399.1:c.1936C>T NP_001395328.1:p.Arg646Ter nonsense NM_001408400.1:c.1936C>T NP_001395329.1:p.Arg646Ter nonsense NM_001408401.1:c.1936C>T NP_001395330.1:p.Arg646Ter nonsense NM_001408402.1:c.1936C>T NP_001395331.1:p.Arg646Ter nonsense NM_001408403.1:c.1936C>T NP_001395332.1:p.Arg646Ter nonsense NM_001408404.1:c.1936C>T NP_001395333.1:p.Arg646Ter nonsense NM_001408406.1:c.1933C>T NP_001395335.1:p.Arg645Ter nonsense NM_001408407.1:c.1933C>T NP_001395336.1:p.Arg645Ter nonsense NM_001408408.1:c.1933C>T NP_001395337.1:p.Arg645Ter nonsense NM_001408409.1:c.1930C>T NP_001395338.1:p.Arg644Ter nonsense NM_001408410.1:c.1867C>T NP_001395339.1:p.Arg623Ter nonsense NM_001408411.1:c.1864C>T NP_001395340.1:p.Arg622Ter nonsense NM_001408412.1:c.1861C>T NP_001395341.1:p.Arg621Ter nonsense NM_001408413.1:c.1861C>T NP_001395342.1:p.Arg621Ter nonsense NM_001408414.1:c.1861C>T NP_001395343.1:p.Arg621Ter nonsense NM_001408415.1:c.1861C>T NP_001395344.1:p.Arg621Ter nonsense NM_001408416.1:c.1861C>T NP_001395345.1:p.Arg621Ter nonsense NM_001408418.1:c.1825C>T NP_001395347.1:p.Arg609Ter nonsense NM_001408419.1:c.1825C>T NP_001395348.1:p.Arg609Ter nonsense NM_001408420.1:c.1825C>T NP_001395349.1:p.Arg609Ter nonsense NM_001408421.1:c.1822C>T NP_001395350.1:p.Arg608Ter nonsense NM_001408422.1:c.1822C>T NP_001395351.1:p.Arg608Ter nonsense NM_001408423.1:c.1822C>T NP_001395352.1:p.Arg608Ter nonsense NM_001408424.1:c.1822C>T NP_001395353.1:p.Arg608Ter nonsense NM_001408425.1:c.1819C>T NP_001395354.1:p.Arg607Ter nonsense NM_001408426.1:c.1819C>T NP_001395355.1:p.Arg607Ter nonsense NM_001408427.1:c.1819C>T NP_001395356.1:p.Arg607Ter nonsense NM_001408428.1:c.1819C>T NP_001395357.1:p.Arg607Ter nonsense NM_001408429.1:c.1819C>T NP_001395358.1:p.Arg607Ter nonsense NM_001408430.1:c.1819C>T NP_001395359.1:p.Arg607Ter nonsense NM_001408431.1:c.1819C>T NP_001395360.1:p.Arg607Ter nonsense NM_001408432.1:c.1816C>T NP_001395361.1:p.Arg606Ter nonsense NM_001408433.1:c.1816C>T NP_001395362.1:p.Arg606Ter nonsense NM_001408434.1:c.1816C>T NP_001395363.1:p.Arg606Ter nonsense NM_001408435.1:c.1816C>T NP_001395364.1:p.Arg606Ter nonsense NM_001408436.1:c.1816C>T NP_001395365.1:p.Arg606Ter nonsense NM_001408437.1:c.1816C>T NP_001395366.1:p.Arg606Ter nonsense NM_001408438.1:c.1816C>T NP_001395367.1:p.Arg606Ter nonsense NM_001408439.1:c.1816C>T NP_001395368.1:p.Arg606Ter nonsense NM_001408440.1:c.1816C>T NP_001395369.1:p.Arg606Ter nonsense NM_001408441.1:c.1816C>T NP_001395370.1:p.Arg606Ter nonsense NM_001408442.1:c.1816C>T NP_001395371.1:p.Arg606Ter nonsense NM_001408443.1:c.1816C>T NP_001395372.1:p.Arg606Ter nonsense NM_001408444.1:c.1816C>T NP_001395373.1:p.Arg606Ter nonsense NM_001408445.1:c.1813C>T NP_001395374.1:p.Arg605Ter nonsense NM_001408446.1:c.1813C>T NP_001395375.1:p.Arg605Ter nonsense NM_001408447.1:c.1813C>T NP_001395376.1:p.Arg605Ter nonsense NM_001408448.1:c.1813C>T NP_001395377.1:p.Arg605Ter nonsense NM_001408450.1:c.1813C>T NP_001395379.1:p.Arg605Ter nonsense NM_001408451.1:c.1807C>T NP_001395380.1:p.Arg603Ter nonsense NM_001408452.1:c.1801C>T NP_001395381.1:p.Arg601Ter nonsense NM_001408453.1:c.1801C>T NP_001395382.1:p.Arg601Ter nonsense NM_001408454.1:c.1801C>T NP_001395383.1:p.Arg601Ter nonsense NM_001408455.1:c.1801C>T NP_001395384.1:p.Arg601Ter nonsense NM_001408456.1:c.1801C>T NP_001395385.1:p.Arg601Ter nonsense NM_001408457.1:c.1801C>T NP_001395386.1:p.Arg601Ter nonsense NM_001408458.1:c.1798C>T NP_001395387.1:p.Arg600Ter nonsense NM_001408459.1:c.1798C>T NP_001395388.1:p.Arg600Ter nonsense NM_001408460.1:c.1798C>T NP_001395389.1:p.Arg600Ter nonsense NM_001408461.1:c.1798C>T NP_001395390.1:p.Arg600Ter nonsense NM_001408462.1:c.1798C>T NP_001395391.1:p.Arg600Ter nonsense NM_001408463.1:c.1798C>T NP_001395392.1:p.Arg600Ter nonsense NM_001408464.1:c.1798C>T NP_001395393.1:p.Arg600Ter nonsense NM_001408465.1:c.1798C>T NP_001395394.1:p.Arg600Ter nonsense NM_001408466.1:c.1798C>T NP_001395395.1:p.Arg600Ter nonsense NM_001408467.1:c.1798C>T NP_001395396.1:p.Arg600Ter nonsense NM_001408468.1:c.1795C>T NP_001395397.1:p.Arg599Ter nonsense NM_001408469.1:c.1795C>T NP_001395398.1:p.Arg599Ter nonsense NM_001408470.1:c.1795C>T NP_001395399.1:p.Arg599Ter nonsense NM_001408472.1:c.1939C>T NP_001395401.1:p.Arg647Ter nonsense NM_001408473.1:c.1936C>T NP_001395402.1:p.Arg646Ter nonsense NM_001408474.1:c.1741C>T NP_001395403.1:p.Arg581Ter nonsense NM_001408475.1:c.1738C>T NP_001395404.1:p.Arg580Ter nonsense NM_001408476.1:c.1738C>T NP_001395405.1:p.Arg580Ter nonsense NM_001408478.1:c.1732C>T NP_001395407.1:p.Arg578Ter nonsense NM_001408479.1:c.1732C>T NP_001395408.1:p.Arg578Ter nonsense NM_001408480.1:c.1732C>T NP_001395409.1:p.Arg578Ter nonsense NM_001408481.1:c.1729C>T NP_001395410.1:p.Arg577Ter nonsense NM_001408482.1:c.1729C>T NP_001395411.1:p.Arg577Ter nonsense NM_001408483.1:c.1729C>T NP_001395412.1:p.Arg577Ter nonsense NM_001408484.1:c.1729C>T NP_001395413.1:p.Arg577Ter nonsense NM_001408485.1:c.1729C>T NP_001395414.1:p.Arg577Ter nonsense NM_001408489.1:c.1729C>T NP_001395418.1:p.Arg577Ter nonsense NM_001408490.1:c.1729C>T NP_001395419.1:p.Arg577Ter nonsense NM_001408491.1:c.1729C>T NP_001395420.1:p.Arg577Ter nonsense NM_001408492.1:c.1726C>T NP_001395421.1:p.Arg576Ter nonsense NM_001408493.1:c.1726C>T NP_001395422.1:p.Arg576Ter nonsense NM_001408494.1:c.1702C>T NP_001395423.1:p.Arg568Ter nonsense NM_001408495.1:c.1696C>T NP_001395424.1:p.Arg566Ter nonsense NM_001408496.1:c.1678C>T NP_001395425.1:p.Arg560Ter nonsense NM_001408497.1:c.1678C>T NP_001395426.1:p.Arg560Ter nonsense NM_001408498.1:c.1678C>T NP_001395427.1:p.Arg560Ter nonsense NM_001408499.1:c.1678C>T NP_001395428.1:p.Arg560Ter nonsense NM_001408500.1:c.1678C>T NP_001395429.1:p.Arg560Ter nonsense NM_001408501.1:c.1678C>T NP_001395430.1:p.Arg560Ter nonsense NM_001408502.1:c.1675C>T NP_001395431.1:p.Arg559Ter nonsense NM_001408503.1:c.1675C>T NP_001395432.1:p.Arg559Ter nonsense NM_001408504.1:c.1675C>T NP_001395433.1:p.Arg559Ter nonsense NM_001408505.1:c.1672C>T NP_001395434.1:p.Arg558Ter nonsense NM_001408506.1:c.1615C>T NP_001395435.1:p.Arg539Ter nonsense NM_001408507.1:c.1612C>T NP_001395436.1:p.Arg538Ter nonsense NM_001408508.1:c.1603C>T NP_001395437.1:p.Arg535Ter nonsense NM_001408509.1:c.1600C>T NP_001395438.1:p.Arg534Ter nonsense NM_001408510.1:c.1561C>T NP_001395439.1:p.Arg521Ter nonsense NM_001408511.1:c.1558C>T NP_001395440.1:p.Arg520Ter nonsense NM_001408512.1:c.1438C>T NP_001395441.1:p.Arg480Ter nonsense NM_001408513.1:c.1411C>T NP_001395442.1:p.Arg471Ter nonsense NM_001408514.1:c.1015C>T NP_001395443.1:p.Arg339Ter nonsense NM_007297.4:c.5110C>T NP_009228.2:p.Arg1704Ter nonsense NM_007298.4:c.1939C>T NP_009229.2:p.Arg647Ter nonsense NM_007299.4:c.1939C>T NP_009230.2:p.Arg647Ter nonsense NM_007300.4:c.5314C>T NP_009231.2:p.Arg1772Ter nonsense NM_007304.2:c.1939C>T NP_009235.2:p.Arg647Ter nonsense NR_027676.2:n.5428C>T non-coding transcript variant NC_000017.11:g.43057078G>A NC_000017.10:g.41209095G>A NG_005905.2:g.160906C>T LRG_292:g.160906C>T LRG_292t1:c.5251C>T LRG_292p1:p.Arg1751Ter U14680.1:n.5370C>T - Protein change
- R1751*, R1772*, R647*, R1704*, R1454*, R1681*, R1682*, R1703*, R1771*, R1773*, R521*, R558*, R566*, R568*, R581*, R599*, R605*, R606*, R622*, R644*, R646*, R1455*, R1582*, R1624*, R1638*, R1639*, R1661*, R1683*, R1684*, R1708*, R1723*, R1725*, R1746*, R1747*, R471*, R480*, R535*, R577*, R601*, R607*, R608*, R621*, R623*, R882*, R1597*, R1662*, R1663*, R1679*, R1702*, R1732*, R1748*, R339*, R538*, R560*, R576*, R603*, R645*, R648*, R670*, R1622*, R1623*, R1640*, R1680*, R1707*, R1709*, R1710*, R1724*, R1731*, R1749*, R1750*, R520*, R534*, R539*, R559*, R578*, R580*, R600*, R609*, R669*, R883*
- Other names
-
p.R1751*:CGA>TGA
5370C>T
- Canonical SPDI
- NC_000017.11:43057077:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
functionally_abnormal; Sequence Ontology [ SO:0002218]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5251C>T, a NONSENSE variant, produced a function score of -1.88, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13041 | 14847 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000048882.33 | |
| Pathogenic (11) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000074600.49 | |
| Pathogenic (21) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000077611.39 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Sep 26, 2022 | RCV000162884.21 | |
| Pathogenic (1) |
criteria provided, single submitter
|
- | RCV000414226.9 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000763399.10 | |
| Pathogenic (1) |
no assertion criteria provided
|
Oct 17, 2018 | RCV000786961.10 | |
| Pathogenic (1) |
no assertion criteria provided
|
Jun 11, 2019 | RCV001270975.9 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282340.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Jul 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743375.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000894125.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
|
Pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000296780.3
First in ClinVar: Jul 01, 2016 Last updated: May 04, 2020 |
Comment:
This is a single base substitution, replacing Arginine with a termination codon. It is expected to result in a truncated, non-functional protein. Truncating variants in … (more)
This is a single base substitution, replacing Arginine with a termination codon. It is expected to result in a truncated, non-functional protein. Truncating variants in BRCA1 are known to be pathogenic. This particular variant is also known as 5370C>T and it has been described in the literature in multiple individuals with breast and ovarian cancer (PMID 21324516, 9361038) and in an individual with prostate cancer (PMID: 27433846). The mutation database ClinVar contains entries for this variant (Variation ID: 55480). (less)
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Molecular Endocrinology Laboratory, Christian Medical College
Accession: SCV002003982.1
First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021 |
|
|
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Pathogenic
(Feb 05, 2022)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002537828.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA1 c.5251C>T (p.R1751X) variant has been reported in heterozygosity in numerous individuals with breast and/or ovarian cancer (PMID: 29310832, 29161300, 30199306). It has been … (more)
The BRCA1 c.5251C>T (p.R1751X) variant has been reported in heterozygosity in numerous individuals with breast and/or ovarian cancer (PMID: 29310832, 29161300, 30199306). It has been reported in a large case-control study of breast cancer in 5/60466 cases and 0/53461 controls (PMID: 33471991). A functional study reported that this variant impacts BRCA1 function in a haploid human cell proliferation assay (PMID: 30209399). This nonsense variant creates a premature stop codon at residue 1751 of the BRCA1 protein. At this location, this variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants in BRCA1 are known to be pathogenic (PMID: 29446198). It was observed in 4/282892 chromosomes in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID 55480). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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|
|
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Pathogenic
(Feb 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002581426.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS3_MOD, PS4_MOD, PM2_SUP
|
Number of individuals with the variant: 1
Sex: female
|
|
|
Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326226.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Mar 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000488332.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Apr 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000108685.16
First in ClinVar: Dec 10, 2013 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Vehmanen 1997, Sarantaus 2001, Stavropoulou 2013, Churpek 2015, Szwiec 2015, Alemar 2016, Pritchard 2016, Brovkina 2018); Published functional studies demonstrate a damaging effect: unable to support viability in a haploid cell line (Findlay 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5370C>T; This variant is associated with the following publications: (PMID: 24528374, 26852015, 27393621, 27514839, 18783588, 17148771, 23199084, 29310832, 21324516, 25525159, 9361038, 26287763, 23536787, 26843898, 26779294, 27167707, 27082205, 27425403, 27756336, 27533253, 27836010, 27433846, 20614009, 24010542, 21232165, 18821011, 16528604, 28324225, 28985766, 23469205, 29339979, 29752822, 29907814, 28993434, 28724667, 22652532, 22434525, 12142080, 11436123, 18159056, 25428789, 17453335, 30209399, 30333958, 31174498, 30702160, 29161300, 30078507, 29446198, 28176296, 30199306, 32295079, 33084842, 30787465, 34011307, 31447099, 32341426, 31825140) (less)
|
|
|
Pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004026749.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
|
|
Pathogenic
(Sep 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Human Genetics Bochum, Ruhr University Bochum
Accession: SCV004042801.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
ACMG criteria used to clasify this variant:PVS1, PS4_MOD, PM2_SUP
|
|
|
Pathogenic
(Sep 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV004183376.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
ACMG classification criteria: PVS1 very strong, PS4 moderated, PM2 moderated
Geographic origin: Brazil
|
|
|
Pathogenic
(Apr 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296322.6
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in multiple individuals and families with breast and/or ovarian cancer or … (more)
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in multiple individuals and families with breast and/or ovarian cancer or prostate cancer in the published literature (PMID: 29752822 (2018), 27433846 (2016), 25428789 (2015), 21324516 (2011), 9361038 (1997)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Dec 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004224783.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP5, PM2, PS3_supporting, PVS1
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Sep 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003809890.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Sep 26, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683276.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 19 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 19 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A functional study reported that this variant impacts BRCA1 function in a haploid human cell proliferation assay (PMID: 30209399). This variant has been reported in over 20 individuals affected with breast and ovarian cancer (PMID: 12142080, 17453335, 18159056, 21324516, 23469205, 23536787, 24010542, 25428789, 26287763, 27393621, 30287823, 32856862, 33471991, 35205313; Leiden Open Variation Database DB-ID BRCA1_000435) and an individual affected with prostate cancer (PMID: 27433846). This variant has been identified in 94 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has been identified in 4/282892 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076895.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1751*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg1751*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357123, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with prostate cancer and breast and ovarian cancer (PMID: 9361038, 21232165, 21324516, 24010542, 25428789, 27433846). This variant is also known as 5370C>T. ClinVar contains an entry for this variant (Variation ID: 55480). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jun 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000605749.4
First in ClinVar: Aug 27, 2017 Last updated: Apr 20, 2024 |
Comment:
The p.Arg1751X variant in BRCA1 has been identified in >50 individuals with BRCA1-associated cancers (Konstantopoulou 2014 PMID: 17453335, Stegal 2011 PMID:21232165, Stavropoulou 2013 PMID: 23536787, … (more)
The p.Arg1751X variant in BRCA1 has been identified in >50 individuals with BRCA1-associated cancers (Konstantopoulou 2014 PMID: 17453335, Stegal 2011 PMID:21232165, Stavropoulou 2013 PMID: 23536787, Breast Cancer Information Core (BIC) database). It has also been identified in 0.005% (1/19954) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was classified as Pathogenic on Apr 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (Variation ID 55480). This nonsense variant leads to a premature termination codon at position 1751, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PS4, PM2. (less)
|
|
|
Pathogenic
(Jan 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004215033.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(May 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199698.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: research
|
Breast Cancer
Affected status: yes
Allele origin:
germline
|
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center
Accession: SCV000492472.1
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
|
|
|
Pathogenic
(Jul 01, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564307.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 10
|
|
|
Pathogenic
(Oct 18, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699227.1
First in ClinVar: Mar 03, 2018 Last updated: Mar 03, 2018 |
Comment:
Variant summary: The BRCA1 c.5251C>T (p.Arg1751X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense … (more)
Variant summary: The BRCA1 c.5251C>T (p.Arg1751X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5266dupC (p.Glh1756fsX74), c.5289delG (p.Leu1764X), and c.5335delC (p.Gln1779fsX14)). The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple databases/clinical diagnostic laboratories cite the variant as "Pathogenic/Causal." Therefore, the variant of interest has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744590.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(May 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839894.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The c.5251C>T (p.Arg1751*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 9361038, 21324516, referred as c.5370C>T] … (more)
The c.5251C>T (p.Arg1751*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 9361038, 21324516, referred as c.5370C>T] and prostate cancer [PMID 27433846]. This variant creates a premature stop codon at amino acid position 1751 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant thus classified as pathogenic. (less)
|
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447498.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Ovarian neoplasm (present)
Sex: female
|
|
|
Pathogenic
(Apr 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499706.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
|
|
Pathogenic
(Dec 14, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
maternal
|
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV002764912.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Number of individuals with the variant: 1
Clinical Features:
Neck muscle weakness (present) , Gait disturbance (present) , Hyperreflexia (present) , Spastic paraplegia (present)
|
|
|
Pathogenic
(May 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
inherited
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004027825.1
First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023 |
Comment:
Criteria applied: PVS1,PS3,PS4,PM2_SUP
Clinical Features:
Family history of cancer (present)
Sex: female
|
|
|
Pathogenic
(Mar 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806683.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
|
|
|
Pathogenic
(Nov 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213371.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.R1751* pathogenic mutation (also known as c.5251C>T), located in coding exon 18 of the BRCA1 gene, results from a C to T substitution at … (more)
The p.R1751* pathogenic mutation (also known as c.5251C>T), located in coding exon 18 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5251. This changes the amino acid from an arginine to a stop codon within coding exon 18. This mutation has been reported in multiple breast and/or ovarian cancer families from various ethnicities to date and has been described as a European founder mutation (Vehmanen P et al. Hum. Mol. Genet. 1997 Dec;6:2309-15; Sinilnikova OM et al. Fam. Cancer. 2006;5:15-20; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504; Janaviius R. EPMA J. 2010 Sep;1:397-412; Stegel V et al. BMC Med. Genet. 2011 Jan;12:9; Zhang S et al. Gynecol. Oncol. 2011 May;121:353-7; Konstantopoulou I et al. Clin. Genet. 2014 Jan;85:36-42; Szwiec M et al. Clin. Genet. 2015 Mar;87:288-92; Zhang J et al. Breast Cancer Res. Treat. 2016 Aug;158:455-62; Alemar B et al. Cancer Genet. 2016 Sep;209:417-422; Rebbeck TR et al. Breast Cancer Res. 2016 Nov;18:112; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295:1227-1238). This mutation has also been reported in gastric cancer patients (awniczak M et al. Hered Cancer Clin Pract. 2016 Jan;14:3), as well as in a study of men with metastatic prostate cancer (Pritchard CC et al. N. Engl. J. Med. 2016 Aug;375:443-53). One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this mutation is also designated as 5370C>T in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Jan 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001747801.20
First in ClinVar: Jul 10, 2021 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Feb 11, 2015)
|
no assertion criteria provided
(clinical testing)
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Medical University Innsbruck
Study: BRCA-Tyrol
Accession: SCV000212009.1 First in ClinVar: Mar 03, 2015 Last updated: Mar 03, 2015
Comment:
BRCA-mutation spectrum Western Austria
|
|
|
|
Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587482.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733592.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Oct 17, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV000925866.1
First in ClinVar: Jul 15, 2019 Last updated: Jul 15, 2019 |
|
|
|
Pathogenic
(Jun 11, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001451780.1
First in ClinVar: Dec 26, 2020 Last updated: Dec 26, 2020 |
Number of individuals with the variant: 2
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
|
|
Pathogenic
(Aug 26, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002588830.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
|
|
|
Pathogenic
(Sep 16, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000109414.5
First in ClinVar: Dec 23, 2013 Last updated: Jun 24, 2016 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591597.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Arg1751X variant has been previously reported in the literature in at least 14 of 6217 individuals with hereditary breast and ovarian cancer and was … (more)
The p.Arg1751X variant has been previously reported in the literature in at least 14 of 6217 individuals with hereditary breast and ovarian cancer and was consistent with a pathogenic role for this variant (Vehmanen 1997, Zhang 2011, Ladopoulou 2002, Schulz 2012, Papi 2009, Risch 2006, Krajc 2008, Sarantaus 2001, Fostira 2012). In a limited number of control chromosomes (186) the variant was not identified in these studies. This variant was also listed in the UMD (13x), LOVD, COSMIC and BIC (33x as clinically important) databases. The p.Arg1751X variant results in a premature stop codon at position 1751, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants in the BRCA1 gene are an established mechanism of hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic. (less)
Number of individuals with the variant: 9
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906148.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952183.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
not provided
(-)
|
no classification provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline,
unknown
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145411.2
First in ClinVar: Apr 01, 2014 Last updated: Mar 03, 2015 |
Observation 1:
Number of individuals with the variant: 17
Observation 2:
Number of individuals with the variant: 3
Geographic origin: Austria
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: African
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: African American
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Austrian
Observation 7:
Number of individuals with the variant: 2
Ethnicity/Population group: Austrian
Geographic origin: Austria
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Greek
Geographic origin: Greece
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Indian
Geographic origin: Malaysia
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Native American, Latin American, Caribbean
Observation 11:
Number of individuals with the variant: 14
Ethnicity/Population group: Western European
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Greek
Observation 13:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Austria
|
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
|
Brotman Baty Institute, University of Washington
Accession: SCV001242472.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-1.87649998421636
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Citation text
Ladopolou-et-al.,-Cancer-Lett,-185:61,-2002
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This is a single base substitution, replacing Arginine with a termination codon. It is expected to result in a truncated, non-functional protein. Truncating variants in BRCA1 are known to be pathogenic. This particular variant is also known as 5370C>T and it has been described in the literature in multiple individuals with breast and ovarian cancer (PMID 21324516, 9361038) and in an individual with prostate cancer (PMID: 27433846). The mutation database ClinVar contains entries for this variant (Variation ID: 55480).
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Vehmanen 1997, Sarantaus 2001, Stavropoulou 2013, Churpek 2015, Szwiec 2015, Alemar 2016, Pritchard 2016, Brovkina 2018); Published functional studies demonstrate a damaging effect: unable to support viability in a haploid cell line (Findlay 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5370C>T; This variant is associated with the following publications: (PMID: 24528374, 26852015, 27393621, 27514839, 18783588, 17148771, 23199084, 29310832, 21324516, 25525159, 9361038, 26287763, 23536787, 26843898, 26779294, 27167707, 27082205, 27425403, 27756336, 27533253, 27836010, 27433846, 20614009, 24010542, 21232165, 18821011, 16528604, 28324225, 28985766, 23469205, 29339979, 29752822, 29907814, 28993434, 28724667, 22652532, 22434525, 12142080, 11436123, 18159056, 25428789, 17453335, 30209399, 30333958, 31174498, 30702160, 29161300, 30078507, 29446198, 28176296, 30199306, 32295079, 33084842, 30787465, 34011307, 31447099, 32341426, 31825140)
Comment:
ACMG criteria used to clasify this variant:PVS1, PS4_MOD, PM2_SUP
Comment:
ACMG classification criteria: PVS1 very strong, PS4 moderated, PM2 moderated
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in multiple individuals and families with breast and/or ovarian cancer or prostate cancer in the published literature (PMID: 29752822 (2018), 27433846 (2016), 25428789 (2015), 21324516 (2011), 9361038 (1997)). Based on the available information, this variant is classified as pathogenic.
Comment:
PP5, PM2, PS3_supporting, PVS1
Comment:
This variant changes 1 nucleotide in exon 19 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A functional study reported that this variant impacts BRCA1 function in a haploid human cell proliferation assay (PMID: 30209399). This variant has been reported in over 20 individuals affected with breast and ovarian cancer (PMID: 12142080, 17453335, 18159056, 21324516, 23469205, 23536787, 24010542, 25428789, 26287763, 27393621, 30287823, 32856862, 33471991, 35205313; Leiden Open Variation Database DB-ID BRCA1_000435) and an individual affected with prostate cancer (PMID: 27433846). This variant has been identified in 94 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has been identified in 4/282892 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Arg1751*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357123, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with prostate cancer and breast and ovarian cancer (PMID: 9361038, 21232165, 21324516, 24010542, 25428789, 27433846). This variant is also known as 5370C>T. ClinVar contains an entry for this variant (Variation ID: 55480). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Arg1751X variant in BRCA1 has been identified in >50 individuals with BRCA1-associated cancers (Konstantopoulou 2014 PMID: 17453335, Stegal 2011 PMID:21232165, Stavropoulou 2013 PMID: 23536787, Breast Cancer Information Core (BIC) database). It has also been identified in 0.005% (1/19954) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was classified as Pathogenic on Apr 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (Variation ID 55480). This nonsense variant leads to a premature termination codon at position 1751, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PS4, PM2.
Comment:
Variant summary: The BRCA1 c.5251C>T (p.Arg1751X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5266dupC (p.Glh1756fsX74), c.5289delG (p.Leu1764X), and c.5335delC (p.Gln1779fsX14)). The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple databases/clinical diagnostic laboratories cite the variant as "Pathogenic/Causal." Therefore, the variant of interest has been classified as Pathogenic.
Comment:
The c.5251C>T (p.Arg1751*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 9361038, 21324516, referred as c.5370C>T] and prostate cancer [PMID 27433846]. This variant creates a premature stop codon at amino acid position 1751 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant thus classified as pathogenic.
Comment:
Criteria applied: PVS1,PS3,PS4,PM2_SUP
Comment:
The p.R1751* pathogenic mutation (also known as c.5251C>T), located in coding exon 18 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5251. This changes the amino acid from an arginine to a stop codon within coding exon 18. This mutation has been reported in multiple breast and/or ovarian cancer families from various ethnicities to date and has been described as a European founder mutation (Vehmanen P et al. Hum. Mol. Genet. 1997 Dec;6:2309-15; Sinilnikova OM et al. Fam. Cancer. 2006;5:15-20; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504; Janaviius R. EPMA J. 2010 Sep;1:397-412; Stegel V et al. BMC Med. Genet. 2011 Jan;12:9; Zhang S et al. Gynecol. Oncol. 2011 May;121:353-7; Konstantopoulou I et al. Clin. Genet. 2014 Jan;85:36-42; Szwiec M et al. Clin. Genet. 2015 Mar;87:288-92; Zhang J et al. Breast Cancer Res. Treat. 2016 Aug;158:455-62; Alemar B et al. Cancer Genet. 2016 Sep;209:417-422; Rebbeck TR et al. Breast Cancer Res. 2016 Nov;18:112; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295:1227-1238). This mutation has also been reported in gastric cancer patients (awniczak M et al. Hered Cancer Clin Pract. 2016 Jan;14:3), as well as in a study of men with metastatic prostate cancer (Pritchard CC et al. N. Engl. J. Med. 2016 Aug;375:443-53). One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this mutation is also designated as 5370C>T in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
The p.Arg1751X variant has been previously reported in the literature in at least 14 of 6217 individuals with hereditary breast and ovarian cancer and was consistent with a pathogenic role for this variant (Vehmanen 1997, Zhang 2011, Ladopoulou 2002, Schulz 2012, Papi 2009, Risch 2006, Krajc 2008, Sarantaus 2001, Fostira 2012). In a limited number of control chromosomes (186) the variant was not identified in these studies. This variant was also listed in the UMD (13x), LOVD, COSMIC and BIC (33x as clinically important) databases. The p.Arg1751X variant results in a premature stop codon at position 1751, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants in the BRCA1 gene are an established mechanism of hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic.
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
|
functionally_abnormal
|
Method citation(s):
|
|
Brotman Baty Institute, University of Washington
Accession: SCV001242472.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5251C>T, a NONSENSE variant, produced a function score of -1.88, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5251C>T, a NONSENSE variant, produced a function score of -1.88, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
|
Citation text
Ladopolou-et-al.,-Cancer-Lett,-185:61,-2002
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This is a single base substitution, replacing Arginine with a termination codon. It is expected to result in a truncated, non-functional protein. Truncating variants in BRCA1 are known to be pathogenic. This particular variant is also known as 5370C>T and it has been described in the literature in multiple individuals with breast and ovarian cancer (PMID 21324516, 9361038) and in an individual with prostate cancer (PMID: 27433846). The mutation database ClinVar contains entries for this variant (Variation ID: 55480).
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Vehmanen 1997, Sarantaus 2001, Stavropoulou 2013, Churpek 2015, Szwiec 2015, Alemar 2016, Pritchard 2016, Brovkina 2018); Published functional studies demonstrate a damaging effect: unable to support viability in a haploid cell line (Findlay 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5370C>T; This variant is associated with the following publications: (PMID: 24528374, 26852015, 27393621, 27514839, 18783588, 17148771, 23199084, 29310832, 21324516, 25525159, 9361038, 26287763, 23536787, 26843898, 26779294, 27167707, 27082205, 27425403, 27756336, 27533253, 27836010, 27433846, 20614009, 24010542, 21232165, 18821011, 16528604, 28324225, 28985766, 23469205, 29339979, 29752822, 29907814, 28993434, 28724667, 22652532, 22434525, 12142080, 11436123, 18159056, 25428789, 17453335, 30209399, 30333958, 31174498, 30702160, 29161300, 30078507, 29446198, 28176296, 30199306, 32295079, 33084842, 30787465, 34011307, 31447099, 32341426, 31825140)
Comment:
ACMG criteria used to clasify this variant:PVS1, PS4_MOD, PM2_SUP
Comment:
ACMG classification criteria: PVS1 very strong, PS4 moderated, PM2 moderated
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. It has been reported in multiple individuals and families with breast and/or ovarian cancer or prostate cancer in the published literature (PMID: 29752822 (2018), 27433846 (2016), 25428789 (2015), 21324516 (2011), 9361038 (1997)). Based on the available information, this variant is classified as pathogenic.
Comment:
PP5, PM2, PS3_supporting, PVS1
Comment:
This variant changes 1 nucleotide in exon 19 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A functional study reported that this variant impacts BRCA1 function in a haploid human cell proliferation assay (PMID: 30209399). This variant has been reported in over 20 individuals affected with breast and ovarian cancer (PMID: 12142080, 17453335, 18159056, 21324516, 23469205, 23536787, 24010542, 25428789, 26287763, 27393621, 30287823, 32856862, 33471991, 35205313; Leiden Open Variation Database DB-ID BRCA1_000435) and an individual affected with prostate cancer (PMID: 27433846). This variant has been identified in 94 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has been identified in 4/282892 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Arg1751*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357123, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with prostate cancer and breast and ovarian cancer (PMID: 9361038, 21232165, 21324516, 24010542, 25428789, 27433846). This variant is also known as 5370C>T. ClinVar contains an entry for this variant (Variation ID: 55480). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Arg1751X variant in BRCA1 has been identified in >50 individuals with BRCA1-associated cancers (Konstantopoulou 2014 PMID: 17453335, Stegal 2011 PMID:21232165, Stavropoulou 2013 PMID: 23536787, Breast Cancer Information Core (BIC) database). It has also been identified in 0.005% (1/19954) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was classified as Pathogenic on Apr 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (Variation ID 55480). This nonsense variant leads to a premature termination codon at position 1751, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PS4, PM2.
Comment:
Variant summary: The BRCA1 c.5251C>T (p.Arg1751X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5266dupC (p.Glh1756fsX74), c.5289delG (p.Leu1764X), and c.5335delC (p.Gln1779fsX14)). The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple databases/clinical diagnostic laboratories cite the variant as "Pathogenic/Causal." Therefore, the variant of interest has been classified as Pathogenic.
Comment:
The c.5251C>T (p.Arg1751*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 9361038, 21324516, referred as c.5370C>T] and prostate cancer [PMID 27433846]. This variant creates a premature stop codon at amino acid position 1751 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant thus classified as pathogenic.
Comment:
Criteria applied: PVS1,PS3,PS4,PM2_SUP
Comment:
The p.R1751* pathogenic mutation (also known as c.5251C>T), located in coding exon 18 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5251. This changes the amino acid from an arginine to a stop codon within coding exon 18. This mutation has been reported in multiple breast and/or ovarian cancer families from various ethnicities to date and has been described as a European founder mutation (Vehmanen P et al. Hum. Mol. Genet. 1997 Dec;6:2309-15; Sinilnikova OM et al. Fam. Cancer. 2006;5:15-20; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504; Janaviius R. EPMA J. 2010 Sep;1:397-412; Stegel V et al. BMC Med. Genet. 2011 Jan;12:9; Zhang S et al. Gynecol. Oncol. 2011 May;121:353-7; Konstantopoulou I et al. Clin. Genet. 2014 Jan;85:36-42; Szwiec M et al. Clin. Genet. 2015 Mar;87:288-92; Zhang J et al. Breast Cancer Res. Treat. 2016 Aug;158:455-62; Alemar B et al. Cancer Genet. 2016 Sep;209:417-422; Rebbeck TR et al. Breast Cancer Res. 2016 Nov;18:112; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295:1227-1238). This mutation has also been reported in gastric cancer patients (awniczak M et al. Hered Cancer Clin Pract. 2016 Jan;14:3), as well as in a study of men with metastatic prostate cancer (Pritchard CC et al. N. Engl. J. Med. 2016 Aug;375:443-53). One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this mutation is also designated as 5370C>T in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
The p.Arg1751X variant has been previously reported in the literature in at least 14 of 6217 individuals with hereditary breast and ovarian cancer and was consistent with a pathogenic role for this variant (Vehmanen 1997, Zhang 2011, Ladopoulou 2002, Schulz 2012, Papi 2009, Risch 2006, Krajc 2008, Sarantaus 2001, Fostira 2012). In a limited number of control chromosomes (186) the variant was not identified in these studies. This variant was also listed in the UMD (13x), LOVD, COSMIC and BIC (33x as clinically important) databases. The p.Arg1751X variant results in a premature stop codon at position 1751, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants in the BRCA1 gene are an established mechanism of hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| BRCA1/2 Mutations in Vietnamese Patients with Hereditary Breast and Ovarian Cancer Syndrome. | Le TN | Genes | 2022 | PMID: 35205313 |
| Genetic testing in women with early-onset breast cancer: a Traceback pilot study. | Augustinsson A | Breast cancer research and treatment | 2021 | PMID: 34529195 |
| Germline mutations in a clinic-based series of pregnancy associated breast cancer patients. | Zografos E | BMC cancer | 2021 | PMID: 34011307 |
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing. | Vu HA | Asian Pacific journal of cancer prevention : APJCP | 2020 | PMID: 32856862 |
| Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer? | Nguyen-Dumont T | Genetics research | 2020 | PMID: 32772980 |
| Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. | De Talhouet S | Scientific reports | 2020 | PMID: 32341426 |
| Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer. | You Y | Frontiers in oncology | 2020 | PMID: 32211327 |
| The spectrum of BRCA1 and BRCA2 mutations and clinicopathological characteristics in Chinese women with early-onset breast cancer. | Chen L | Breast cancer research and treatment | 2020 | PMID: 32072338 |
| Comprehensive mutation detection of BRCA1/2 genes reveals large genomic rearrangements contribute to hereditary breast and ovarian cancer in Chinese women. | Cao WM | BMC cancer | 2019 | PMID: 31174498 |
| Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
| Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
| Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer. | Abulkhair O | Journal of global oncology | 2018 | PMID: 30199306 |
| BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Pathogenic Germline Variants in 10,389 Adult Cancers. | Huang KL | Cell | 2018 | PMID: 29625052 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
| Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center. | Apessos A | Cancer genetics | 2018 | PMID: 29310832 |
| Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia. | Wen WX | Journal of medical genetics | 2018 | PMID: 28993434 |
| BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil: Are international testing criteria appropriate for this specific population? | Alemar B | PloS one | 2017 | PMID: 29161300 |
| Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. | Lilyquist J | Gynecologic oncology | 2017 | PMID: 28888541 |
| Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
| Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
| Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. | Rebbeck TR | Breast cancer research : BCR | 2016 | PMID: 27836010 |
| Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry. | Fernandes GC | Oncotarget | 2016 | PMID: 27741520 |
| Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. | Pritchard CC | The New England journal of medicine | 2016 | PMID: 27433846 |
| Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. | Alemar B | Cancer genetics | 2016 | PMID: 27425403 |
| Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer. | Zhang J | Breast cancer research and treatment | 2016 | PMID: 27393621 |
| Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland. | Wojcik P | Hereditary cancer in clinical practice | 2016 | PMID: 26843898 |
| BRCA1 founder mutations do not contribute to increased risk of gastric cancer in the Polish population. | Ławniczak M | Hereditary cancer in clinical practice | 2016 | PMID: 26779294 |
| A high frequency of BRCA mutations in young black women with breast cancer residing in Florida. | Pal T | Cancer | 2015 | PMID: 26287763 |
| RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
| Inherited predisposition to breast cancer among African American women. | Churpek JE | Breast cancer research and treatment | 2015 | PMID: 25428789 |
| Recurrent mutations of BRCA1 and BRCA2 in Poland: an update. | Szwiec M | Clinical genetics | 2015 | PMID: 24528374 |
| High prevalence of BRCA1 founder mutations in Greek breast/ovarian families. | Konstantopoulou I | Clinical genetics | 2014 | PMID: 24010542 |
| Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases. | Stavropoulou AV | PloS one | 2013 | PMID: 23536787 |
| Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil. | Carraro DM | PloS one | 2013 | PMID: 23469205 |
| Germline mutations in the DNA damage response genes BRCA1, BRCA2, BARD1 and TP53 in patients with therapy related myeloid neoplasms. | Schulz E | Journal of medical genetics | 2012 | PMID: 22652532 |
| Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
| The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population. | Stegel V | BMC medical genetics | 2011 | PMID: 21232165 |
| Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. | Janavičius R | The EPMA journal | 2010 | PMID: 23199084 |
| Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function. | Guendel I | PloS one | 2010 | PMID: 20614009 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy. | Papi L | Breast cancer research and treatment | 2009 | PMID: 18821011 |
| Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients. | Konstantopoulou I | Breast cancer research and treatment | 2008 | PMID: 17453335 |
| Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. | John EM | JAMA | 2007 | PMID: 18159056 |
| BRCA1 and BRCA2 mutations in breast and ovarian cancer syndrome: reflection on the Creighton University historical series of high risk families. | Sinilnikova OM | Familial cancer | 2006 | PMID: 16528604 |
| Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed. | Ladopoulou A | Cancer letters | 2002 | PMID: 12142080 |
| Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes. | Vehmanen P | Human molecular genetics | 1997 | PMID: 9361038 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
| Wagner et al. Int. J. Cancer, in press | - | - | - | - |
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Record last updated Nov 03, 2024
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