ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5504G>A (p.Arg1835Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(9); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5504G>A (p.Arg1835Gln)
Variation ID: 55604 Accession: VCV000055604.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045766 (GRCh38) [ NCBI UCSC ] 17: 41197783 (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 Apr 1, 2014 May 1, 2024 Jan 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5504G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Arg1835Gln missense NM_001407571.1:c.5291G>A NP_001394500.1:p.Arg1764Gln missense NM_001407581.1:c.5570G>A NP_001394510.1:p.Arg1857Gln missense NM_001407582.1:c.5570G>A NP_001394511.1:p.Arg1857Gln missense NM_001407583.1:c.5567G>A NP_001394512.1:p.Arg1856Gln missense NM_001407585.1:c.5567G>A NP_001394514.1:p.Arg1856Gln missense NM_001407587.1:c.5567G>A NP_001394516.1:p.Arg1856Gln missense NM_001407590.1:c.5564G>A NP_001394519.1:p.Arg1855Gln missense NM_001407591.1:c.5564G>A NP_001394520.1:p.Arg1855Gln missense NM_001407593.1:c.5504G>A NP_001394522.1:p.Arg1835Gln missense NM_001407594.1:c.5504G>A NP_001394523.1:p.Arg1835Gln missense NM_001407596.1:c.5504G>A NP_001394525.1:p.Arg1835Gln missense NM_001407597.1:c.5504G>A NP_001394526.1:p.Arg1835Gln missense NM_001407598.1:c.5504G>A NP_001394527.1:p.Arg1835Gln missense NM_001407602.1:c.5504G>A NP_001394531.1:p.Arg1835Gln missense NM_001407603.1:c.5504G>A NP_001394532.1:p.Arg1835Gln missense NM_001407605.1:c.5504G>A NP_001394534.1:p.Arg1835Gln missense NM_001407610.1:c.5501G>A NP_001394539.1:p.Arg1834Gln missense NM_001407611.1:c.5501G>A NP_001394540.1:p.Arg1834Gln missense NM_001407612.1:c.5501G>A NP_001394541.1:p.Arg1834Gln missense NM_001407613.1:c.5501G>A NP_001394542.1:p.Arg1834Gln missense NM_001407614.1:c.5501G>A NP_001394543.1:p.Arg1834Gln missense NM_001407615.1:c.5501G>A NP_001394544.1:p.Arg1834Gln missense NM_001407616.1:c.5501G>A NP_001394545.1:p.Arg1834Gln missense NM_001407617.1:c.5501G>A NP_001394546.1:p.Arg1834Gln missense NM_001407618.1:c.5501G>A NP_001394547.1:p.Arg1834Gln missense NM_001407619.1:c.5501G>A NP_001394548.1:p.Arg1834Gln missense NM_001407620.1:c.5501G>A NP_001394549.1:p.Arg1834Gln missense NM_001407621.1:c.5501G>A NP_001394550.1:p.Arg1834Gln missense NM_001407622.1:c.5501G>A NP_001394551.1:p.Arg1834Gln missense NM_001407623.1:c.5501G>A NP_001394552.1:p.Arg1834Gln missense NM_001407624.1:c.5501G>A NP_001394553.1:p.Arg1834Gln missense NM_001407625.1:c.5501G>A NP_001394554.1:p.Arg1834Gln missense NM_001407626.1:c.5501G>A NP_001394555.1:p.Arg1834Gln missense NM_001407627.1:c.5498G>A NP_001394556.1:p.Arg1833Gln missense NM_001407628.1:c.5498G>A NP_001394557.1:p.Arg1833Gln missense NM_001407629.1:c.5498G>A NP_001394558.1:p.Arg1833Gln missense NM_001407630.1:c.5498G>A NP_001394559.1:p.Arg1833Gln missense NM_001407631.1:c.5498G>A NP_001394560.1:p.Arg1833Gln missense NM_001407632.1:c.5498G>A NP_001394561.1:p.Arg1833Gln missense NM_001407633.1:c.5498G>A NP_001394562.1:p.Arg1833Gln missense NM_001407634.1:c.5498G>A NP_001394563.1:p.Arg1833Gln missense NM_001407635.1:c.5498G>A NP_001394564.1:p.Arg1833Gln missense NM_001407636.1:c.5498G>A NP_001394565.1:p.Arg1833Gln missense NM_001407637.1:c.5498G>A NP_001394566.1:p.Arg1833Gln missense NM_001407638.1:c.5498G>A NP_001394567.1:p.Arg1833Gln missense NM_001407639.1:c.5498G>A NP_001394568.1:p.Arg1833Gln missense NM_001407640.1:c.5498G>A NP_001394569.1:p.Arg1833Gln missense NM_001407641.1:c.5498G>A NP_001394570.1:p.Arg1833Gln missense NM_001407642.1:c.5498G>A NP_001394571.1:p.Arg1833Gln missense NM_001407644.1:c.5495G>A NP_001394573.1:p.Arg1832Gln missense NM_001407645.1:c.5495G>A NP_001394574.1:p.Arg1832Gln missense NM_001407646.1:c.5492G>A NP_001394575.1:p.Arg1831Gln missense NM_001407647.1:c.5489G>A NP_001394576.1:p.Arg1830Gln missense NM_001407648.1:c.5447G>A NP_001394577.1:p.Arg1816Gln missense NM_001407649.1:c.5444G>A NP_001394578.1:p.Arg1815Gln missense NM_001407652.1:c.5426G>A NP_001394581.1:p.Arg1809Gln missense NM_001407653.1:c.5426G>A NP_001394582.1:p.Arg1809Gln missense NM_001407654.1:c.5426G>A NP_001394583.1:p.Arg1809Gln missense NM_001407655.1:c.5426G>A NP_001394584.1:p.Arg1809Gln missense NM_001407656.1:c.5423G>A NP_001394585.1:p.Arg1808Gln missense NM_001407657.1:c.5423G>A NP_001394586.1:p.Arg1808Gln missense NM_001407658.1:c.5423G>A NP_001394587.1:p.Arg1808Gln missense NM_001407659.1:c.5420G>A NP_001394588.1:p.Arg1807Gln missense NM_001407660.1:c.5420G>A NP_001394589.1:p.Arg1807Gln missense NM_001407661.1:c.5420G>A NP_001394590.1:p.Arg1807Gln missense NM_001407662.1:c.5420G>A NP_001394591.1:p.Arg1807Gln missense NM_001407663.1:c.5420G>A NP_001394592.1:p.Arg1807Gln missense NM_001407664.1:c.5381G>A NP_001394593.1:p.Arg1794Gln missense NM_001407665.1:c.5381G>A NP_001394594.1:p.Arg1794Gln missense NM_001407666.1:c.5381G>A NP_001394595.1:p.Arg1794Gln missense NM_001407667.1:c.5381G>A NP_001394596.1:p.Arg1794Gln missense NM_001407668.1:c.5381G>A NP_001394597.1:p.Arg1794Gln missense NM_001407669.1:c.5381G>A NP_001394598.1:p.Arg1794Gln missense NM_001407670.1:c.5378G>A NP_001394599.1:p.Arg1793Gln missense NM_001407671.1:c.5378G>A NP_001394600.1:p.Arg1793Gln missense NM_001407672.1:c.5378G>A NP_001394601.1:p.Arg1793Gln missense NM_001407673.1:c.5378G>A NP_001394602.1:p.Arg1793Gln missense NM_001407674.1:c.5378G>A NP_001394603.1:p.Arg1793Gln missense NM_001407675.1:c.5378G>A NP_001394604.1:p.Arg1793Gln missense NM_001407676.1:c.5378G>A NP_001394605.1:p.Arg1793Gln missense NM_001407677.1:c.5378G>A NP_001394606.1:p.Arg1793Gln missense NM_001407678.1:c.5378G>A NP_001394607.1:p.Arg1793Gln missense NM_001407679.1:c.5378G>A NP_001394608.1:p.Arg1793Gln missense NM_001407680.1:c.5378G>A NP_001394609.1:p.Arg1793Gln missense NM_001407681.1:c.5375G>A NP_001394610.1:p.Arg1792Gln missense NM_001407682.1:c.5375G>A NP_001394611.1:p.Arg1792Gln missense NM_001407683.1:c.5375G>A NP_001394612.1:p.Arg1792Gln missense NM_001407684.1:c.5375G>A NP_001394613.1:p.Arg1792Gln missense NM_001407685.1:c.5375G>A NP_001394614.1:p.Arg1792Gln missense NM_001407686.1:c.5375G>A NP_001394615.1:p.Arg1792Gln missense NM_001407687.1:c.5375G>A NP_001394616.1:p.Arg1792Gln missense NM_001407688.1:c.5375G>A NP_001394617.1:p.Arg1792Gln missense NM_001407689.1:c.5375G>A NP_001394618.1:p.Arg1792Gln missense NM_001407690.1:c.5372G>A NP_001394619.1:p.Arg1791Gln missense NM_001407691.1:c.5372G>A NP_001394620.1:p.Arg1791Gln missense NM_001407692.1:c.5363G>A NP_001394621.1:p.Arg1788Gln missense NM_001407694.1:c.5363G>A NP_001394623.1:p.Arg1788Gln missense NM_001407695.1:c.5363G>A NP_001394624.1:p.Arg1788Gln missense NM_001407696.1:c.5363G>A NP_001394625.1:p.Arg1788Gln missense NM_001407697.1:c.5363G>A NP_001394626.1:p.Arg1788Gln missense NM_001407698.1:c.5363G>A NP_001394627.1:p.Arg1788Gln missense NM_001407724.1:c.5363G>A NP_001394653.1:p.Arg1788Gln missense NM_001407725.1:c.5363G>A NP_001394654.1:p.Arg1788Gln missense NM_001407726.1:c.5363G>A NP_001394655.1:p.Arg1788Gln missense NM_001407727.1:c.5363G>A NP_001394656.1:p.Arg1788Gln missense NM_001407728.1:c.5363G>A NP_001394657.1:p.Arg1788Gln missense NM_001407729.1:c.5363G>A NP_001394658.1:p.Arg1788Gln missense NM_001407730.1:c.5363G>A NP_001394659.1:p.Arg1788Gln missense NM_001407731.1:c.5363G>A NP_001394660.1:p.Arg1788Gln missense NM_001407732.1:c.5360G>A NP_001394661.1:p.Arg1787Gln missense NM_001407733.1:c.5360G>A NP_001394662.1:p.Arg1787Gln missense NM_001407734.1:c.5360G>A NP_001394663.1:p.Arg1787Gln missense NM_001407735.1:c.5360G>A NP_001394664.1:p.Arg1787Gln missense NM_001407736.1:c.5360G>A NP_001394665.1:p.Arg1787Gln missense NM_001407737.1:c.5360G>A NP_001394666.1:p.Arg1787Gln missense NM_001407738.1:c.5360G>A NP_001394667.1:p.Arg1787Gln missense NM_001407739.1:c.5360G>A NP_001394668.1:p.Arg1787Gln missense NM_001407740.1:c.5360G>A NP_001394669.1:p.Arg1787Gln missense NM_001407741.1:c.5360G>A NP_001394670.1:p.Arg1787Gln missense NM_001407742.1:c.5360G>A NP_001394671.1:p.Arg1787Gln missense NM_001407743.1:c.5360G>A NP_001394672.1:p.Arg1787Gln missense NM_001407744.1:c.5360G>A NP_001394673.1:p.Arg1787Gln missense NM_001407745.1:c.5360G>A NP_001394674.1:p.Arg1787Gln missense NM_001407746.1:c.5360G>A NP_001394675.1:p.Arg1787Gln missense NM_001407747.1:c.5360G>A NP_001394676.1:p.Arg1787Gln missense NM_001407748.1:c.5360G>A NP_001394677.1:p.Arg1787Gln missense NM_001407749.1:c.5360G>A NP_001394678.1:p.Arg1787Gln missense NM_001407750.1:c.5360G>A NP_001394679.1:p.Arg1787Gln missense NM_001407751.1:c.5360G>A NP_001394680.1:p.Arg1787Gln missense NM_001407752.1:c.5360G>A NP_001394681.1:p.Arg1787Gln missense NM_001407838.1:c.5357G>A NP_001394767.1:p.Arg1786Gln missense NM_001407839.1:c.5357G>A NP_001394768.1:p.Arg1786Gln missense NM_001407841.1:c.5357G>A NP_001394770.1:p.Arg1786Gln missense NM_001407842.1:c.5357G>A NP_001394771.1:p.Arg1786Gln missense NM_001407843.1:c.5357G>A NP_001394772.1:p.Arg1786Gln missense NM_001407844.1:c.5357G>A NP_001394773.1:p.Arg1786Gln missense NM_001407845.1:c.5357G>A NP_001394774.1:p.Arg1786Gln missense NM_001407846.1:c.5357G>A NP_001394775.1:p.Arg1786Gln missense NM_001407847.1:c.5357G>A NP_001394776.1:p.Arg1786Gln missense NM_001407848.1:c.5357G>A NP_001394777.1:p.Arg1786Gln missense NM_001407849.1:c.5357G>A NP_001394778.1:p.Arg1786Gln missense NM_001407850.1:c.5357G>A NP_001394779.1:p.Arg1786Gln missense NM_001407851.1:c.5357G>A NP_001394780.1:p.Arg1786Gln missense NM_001407852.1:c.5357G>A NP_001394781.1:p.Arg1786Gln missense NM_001407853.1:c.5357G>A NP_001394782.1:p.Arg1786Gln missense NM_001407854.1:c.*18G>A NM_001407858.1:c.*18G>A NM_001407859.1:c.*18G>A NM_001407860.1:c.*18G>A NM_001407861.1:c.*18G>A NM_001407862.1:c.5303G>A NP_001394791.1:p.Arg1768Gln missense NM_001407863.1:c.5300G>A NP_001394792.1:p.Arg1767Gln missense NM_001407874.1:c.5297G>A NP_001394803.1:p.Arg1766Gln missense NM_001407875.1:c.5297G>A NP_001394804.1:p.Arg1766Gln missense NM_001407879.1:c.5294G>A NP_001394808.1:p.Arg1765Gln missense NM_001407881.1:c.5294G>A NP_001394810.1:p.Arg1765Gln missense NM_001407882.1:c.5294G>A NP_001394811.1:p.Arg1765Gln missense NM_001407884.1:c.5294G>A NP_001394813.1:p.Arg1765Gln missense NM_001407885.1:c.5294G>A NP_001394814.1:p.Arg1765Gln missense NM_001407886.1:c.5294G>A NP_001394815.1:p.Arg1765Gln missense NM_001407887.1:c.5294G>A NP_001394816.1:p.Arg1765Gln missense NM_001407889.1:c.5294G>A NP_001394818.1:p.Arg1765Gln missense NM_001407894.1:c.5291G>A NP_001394823.1:p.Arg1764Gln missense NM_001407895.1:c.5291G>A NP_001394824.1:p.Arg1764Gln missense NM_001407896.1:c.5291G>A NP_001394825.1:p.Arg1764Gln missense NM_001407897.1:c.5291G>A NP_001394826.1:p.Arg1764Gln missense NM_001407898.1:c.5291G>A NP_001394827.1:p.Arg1764Gln missense NM_001407899.1:c.5291G>A NP_001394828.1:p.Arg1764Gln missense NM_001407900.1:c.5291G>A NP_001394829.1:p.Arg1764Gln missense NM_001407902.1:c.5291G>A NP_001394831.1:p.Arg1764Gln missense NM_001407904.1:c.5291G>A NP_001394833.1:p.Arg1764Gln missense NM_001407906.1:c.5291G>A NP_001394835.1:p.Arg1764Gln missense NM_001407907.1:c.5291G>A NP_001394836.1:p.Arg1764Gln missense NM_001407908.1:c.5291G>A NP_001394837.1:p.Arg1764Gln missense NM_001407909.1:c.5291G>A NP_001394838.1:p.Arg1764Gln missense NM_001407910.1:c.5291G>A NP_001394839.1:p.Arg1764Gln missense NM_001407915.1:c.5288G>A NP_001394844.1:p.Arg1763Gln missense NM_001407916.1:c.5288G>A NP_001394845.1:p.Arg1763Gln missense NM_001407917.1:c.5288G>A NP_001394846.1:p.Arg1763Gln missense NM_001407918.1:c.5288G>A NP_001394847.1:p.Arg1763Gln missense NM_001407919.1:c.5252G>A NP_001394848.1:p.Arg1751Gln missense NM_001407920.1:c.5240G>A NP_001394849.1:p.Arg1747Gln missense NM_001407921.1:c.5240G>A NP_001394850.1:p.Arg1747Gln missense NM_001407922.1:c.5240G>A NP_001394851.1:p.Arg1747Gln missense NM_001407923.1:c.5240G>A NP_001394852.1:p.Arg1747Gln missense NM_001407924.1:c.5240G>A NP_001394853.1:p.Arg1747Gln missense NM_001407925.1:c.5240G>A NP_001394854.1:p.Arg1747Gln missense NM_001407926.1:c.5240G>A NP_001394855.1:p.Arg1747Gln missense NM_001407927.1:c.5237G>A NP_001394856.1:p.Arg1746Gln missense NM_001407928.1:c.5237G>A NP_001394857.1:p.Arg1746Gln missense NM_001407929.1:c.5237G>A NP_001394858.1:p.Arg1746Gln missense NM_001407930.1:c.5237G>A NP_001394859.1:p.Arg1746Gln missense NM_001407931.1:c.5237G>A NP_001394860.1:p.Arg1746Gln missense NM_001407932.1:c.5237G>A NP_001394861.1:p.Arg1746Gln missense NM_001407933.1:c.5237G>A NP_001394862.1:p.Arg1746Gln missense NM_001407934.1:c.5234G>A NP_001394863.1:p.Arg1745Gln missense NM_001407935.1:c.5234G>A NP_001394864.1:p.Arg1745Gln missense NM_001407936.1:c.5234G>A NP_001394865.1:p.Arg1745Gln missense NM_001407937.1:c.*18G>A NM_001407938.1:c.*18G>A NM_001407939.1:c.*18G>A NM_001407940.1:c.*18G>A NM_001407941.1:c.*18G>A NM_001407942.1:c.*18G>A NM_001407943.1:c.*18G>A NM_001407944.1:c.*18G>A NM_001407945.1:c.*18G>A NM_001407946.1:c.5171G>A NP_001394875.1:p.Arg1724Gln missense NM_001407947.1:c.5171G>A NP_001394876.1:p.Arg1724Gln missense NM_001407948.1:c.5171G>A NP_001394877.1:p.Arg1724Gln missense NM_001407949.1:c.5171G>A NP_001394878.1:p.Arg1724Gln missense NM_001407950.1:c.5168G>A NP_001394879.1:p.Arg1723Gln missense NM_001407951.1:c.5168G>A NP_001394880.1:p.Arg1723Gln missense NM_001407952.1:c.5168G>A NP_001394881.1:p.Arg1723Gln missense NM_001407953.1:c.5168G>A NP_001394882.1:p.Arg1723Gln missense NM_001407954.1:c.5168G>A NP_001394883.1:p.Arg1723Gln missense NM_001407955.1:c.5168G>A NP_001394884.1:p.Arg1723Gln missense NM_001407956.1:c.5165G>A NP_001394885.1:p.Arg1722Gln missense NM_001407957.1:c.5165G>A NP_001394886.1:p.Arg1722Gln missense NM_001407958.1:c.5165G>A NP_001394887.1:p.Arg1722Gln missense NM_001407959.1:c.5123G>A NP_001394888.1:p.Arg1708Gln missense NM_001407960.1:c.5120G>A NP_001394889.1:p.Arg1707Gln missense NM_001407962.1:c.5120G>A NP_001394891.1:p.Arg1707Gln missense NM_001407963.1:c.5117G>A NP_001394892.1:p.Arg1706Gln missense NM_001407964.1:c.5042G>A NP_001394893.1:p.Arg1681Gln missense NM_001407965.1:c.4997G>A NP_001394894.1:p.Arg1666Gln missense NM_001407966.1:c.4616G>A NP_001394895.1:p.Arg1539Gln missense NM_001407967.1:c.4613G>A NP_001394896.1:p.Arg1538Gln missense NM_001407968.1:c.2900G>A NP_001394897.1:p.Arg967Gln missense NM_001407969.1:c.2897G>A NP_001394898.1:p.Arg966Gln missense NM_001407970.1:c.2261G>A NP_001394899.1:p.Arg754Gln missense NM_001407971.1:c.2261G>A NP_001394900.1:p.Arg754Gln missense NM_001407972.1:c.2258G>A NP_001394901.1:p.Arg753Gln missense NM_001407973.1:c.2195G>A NP_001394902.1:p.Arg732Gln missense NM_001407974.1:c.2195G>A NP_001394903.1:p.Arg732Gln missense NM_001407975.1:c.2195G>A NP_001394904.1:p.Arg732Gln missense NM_001407976.1:c.2195G>A NP_001394905.1:p.Arg732Gln missense NM_001407977.1:c.2195G>A NP_001394906.1:p.Arg732Gln missense NM_001407978.1:c.2195G>A NP_001394907.1:p.Arg732Gln missense NM_001407979.1:c.2192G>A NP_001394908.1:p.Arg731Gln missense NM_001407980.1:c.2192G>A NP_001394909.1:p.Arg731Gln missense NM_001407981.1:c.2192G>A NP_001394910.1:p.Arg731Gln missense NM_001407982.1:c.2192G>A NP_001394911.1:p.Arg731Gln missense NM_001407983.1:c.2192G>A NP_001394912.1:p.Arg731Gln missense NM_001407984.1:c.2192G>A NP_001394913.1:p.Arg731Gln missense NM_001407985.1:c.2192G>A NP_001394914.1:p.Arg731Gln missense NM_001407986.1:c.2192G>A NP_001394915.1:p.Arg731Gln missense NM_001407990.1:c.2192G>A NP_001394919.1:p.Arg731Gln missense NM_001407991.1:c.2192G>A NP_001394920.1:p.Arg731Gln missense NM_001407992.1:c.2192G>A NP_001394921.1:p.Arg731Gln missense NM_001407993.1:c.2192G>A NP_001394922.1:p.Arg731Gln missense NM_001408392.1:c.2189G>A NP_001395321.1:p.Arg730Gln missense NM_001408396.1:c.2189G>A NP_001395325.1:p.Arg730Gln missense NM_001408397.1:c.2189G>A NP_001395326.1:p.Arg730Gln missense NM_001408398.1:c.2189G>A NP_001395327.1:p.Arg730Gln missense NM_001408399.1:c.2189G>A NP_001395328.1:p.Arg730Gln missense NM_001408400.1:c.2189G>A NP_001395329.1:p.Arg730Gln missense NM_001408401.1:c.2189G>A NP_001395330.1:p.Arg730Gln missense NM_001408402.1:c.2189G>A NP_001395331.1:p.Arg730Gln missense NM_001408403.1:c.2189G>A NP_001395332.1:p.Arg730Gln missense NM_001408404.1:c.2189G>A NP_001395333.1:p.Arg730Gln missense NM_001408406.1:c.2186G>A NP_001395335.1:p.Arg729Gln missense NM_001408407.1:c.2186G>A NP_001395336.1:p.Arg729Gln missense NM_001408408.1:c.2186G>A NP_001395337.1:p.Arg729Gln missense NM_001408409.1:c.2183G>A NP_001395338.1:p.Arg728Gln missense NM_001408410.1:c.2120G>A NP_001395339.1:p.Arg707Gln missense NM_001408411.1:c.2117G>A NP_001395340.1:p.Arg706Gln missense NM_001408412.1:c.2114G>A NP_001395341.1:p.Arg705Gln missense NM_001408413.1:c.2114G>A NP_001395342.1:p.Arg705Gln missense NM_001408414.1:c.2114G>A NP_001395343.1:p.Arg705Gln missense NM_001408415.1:c.2114G>A NP_001395344.1:p.Arg705Gln missense NM_001408416.1:c.2114G>A NP_001395345.1:p.Arg705Gln missense NM_001408418.1:c.2078G>A NP_001395347.1:p.Arg693Gln missense NM_001408419.1:c.2078G>A NP_001395348.1:p.Arg693Gln missense NM_001408420.1:c.2078G>A NP_001395349.1:p.Arg693Gln missense NM_001408421.1:c.2075G>A NP_001395350.1:p.Arg692Gln missense NM_001408422.1:c.2075G>A NP_001395351.1:p.Arg692Gln missense NM_001408423.1:c.2075G>A NP_001395352.1:p.Arg692Gln missense NM_001408424.1:c.2075G>A NP_001395353.1:p.Arg692Gln missense NM_001408425.1:c.2072G>A NP_001395354.1:p.Arg691Gln missense NM_001408426.1:c.2072G>A NP_001395355.1:p.Arg691Gln missense NM_001408427.1:c.2072G>A NP_001395356.1:p.Arg691Gln missense NM_001408428.1:c.2072G>A NP_001395357.1:p.Arg691Gln missense NM_001408429.1:c.2072G>A NP_001395358.1:p.Arg691Gln missense NM_001408430.1:c.2072G>A NP_001395359.1:p.Arg691Gln missense NM_001408431.1:c.2072G>A NP_001395360.1:p.Arg691Gln missense NM_001408432.1:c.2069G>A NP_001395361.1:p.Arg690Gln missense NM_001408433.1:c.2069G>A NP_001395362.1:p.Arg690Gln missense NM_001408434.1:c.2069G>A NP_001395363.1:p.Arg690Gln missense NM_001408435.1:c.2069G>A NP_001395364.1:p.Arg690Gln missense NM_001408436.1:c.2069G>A NP_001395365.1:p.Arg690Gln missense NM_001408437.1:c.2069G>A NP_001395366.1:p.Arg690Gln missense NM_001408438.1:c.2069G>A NP_001395367.1:p.Arg690Gln missense NM_001408439.1:c.2069G>A NP_001395368.1:p.Arg690Gln missense NM_001408440.1:c.2069G>A NP_001395369.1:p.Arg690Gln missense NM_001408441.1:c.2069G>A NP_001395370.1:p.Arg690Gln missense NM_001408442.1:c.2069G>A NP_001395371.1:p.Arg690Gln missense NM_001408443.1:c.2069G>A NP_001395372.1:p.Arg690Gln missense NM_001408444.1:c.2069G>A NP_001395373.1:p.Arg690Gln missense NM_001408445.1:c.2066G>A NP_001395374.1:p.Arg689Gln missense NM_001408446.1:c.2066G>A NP_001395375.1:p.Arg689Gln missense NM_001408447.1:c.2066G>A NP_001395376.1:p.Arg689Gln missense NM_001408448.1:c.2066G>A NP_001395377.1:p.Arg689Gln missense NM_001408450.1:c.2066G>A NP_001395379.1:p.Arg689Gln missense NM_001408451.1:c.2060G>A NP_001395380.1:p.Arg687Gln missense NM_001408452.1:c.2054G>A NP_001395381.1:p.Arg685Gln missense NM_001408453.1:c.2054G>A NP_001395382.1:p.Arg685Gln missense NM_001408454.1:c.2054G>A NP_001395383.1:p.Arg685Gln missense NM_001408455.1:c.2054G>A NP_001395384.1:p.Arg685Gln missense NM_001408456.1:c.2054G>A NP_001395385.1:p.Arg685Gln missense NM_001408457.1:c.2054G>A NP_001395386.1:p.Arg685Gln missense NM_001408458.1:c.2051G>A NP_001395387.1:p.Arg684Gln missense NM_001408459.1:c.2051G>A NP_001395388.1:p.Arg684Gln missense NM_001408460.1:c.2051G>A NP_001395389.1:p.Arg684Gln missense NM_001408461.1:c.2051G>A NP_001395390.1:p.Arg684Gln missense NM_001408462.1:c.2051G>A NP_001395391.1:p.Arg684Gln missense NM_001408463.1:c.2051G>A NP_001395392.1:p.Arg684Gln missense NM_001408464.1:c.2051G>A NP_001395393.1:p.Arg684Gln missense NM_001408465.1:c.2051G>A NP_001395394.1:p.Arg684Gln missense NM_001408466.1:c.2051G>A NP_001395395.1:p.Arg684Gln missense NM_001408467.1:c.2051G>A NP_001395396.1:p.Arg684Gln missense NM_001408468.1:c.2048G>A NP_001395397.1:p.Arg683Gln missense NM_001408469.1:c.2048G>A NP_001395398.1:p.Arg683Gln missense NM_001408470.1:c.2048G>A NP_001395399.1:p.Arg683Gln missense NM_001408472.1:c.*18G>A NM_001408473.1:c.*18G>A NM_001408474.1:c.1994G>A NP_001395403.1:p.Arg665Gln missense NM_001408475.1:c.1991G>A NP_001395404.1:p.Arg664Gln missense NM_001408476.1:c.1991G>A NP_001395405.1:p.Arg664Gln missense NM_001408478.1:c.1985G>A NP_001395407.1:p.Arg662Gln missense NM_001408479.1:c.1985G>A NP_001395408.1:p.Arg662Gln missense NM_001408480.1:c.1985G>A NP_001395409.1:p.Arg662Gln missense NM_001408481.1:c.1982G>A NP_001395410.1:p.Arg661Gln missense NM_001408482.1:c.1982G>A NP_001395411.1:p.Arg661Gln missense NM_001408483.1:c.1982G>A NP_001395412.1:p.Arg661Gln missense NM_001408484.1:c.1982G>A NP_001395413.1:p.Arg661Gln missense NM_001408485.1:c.1982G>A NP_001395414.1:p.Arg661Gln missense NM_001408489.1:c.1982G>A NP_001395418.1:p.Arg661Gln missense NM_001408490.1:c.1982G>A NP_001395419.1:p.Arg661Gln missense NM_001408491.1:c.1982G>A NP_001395420.1:p.Arg661Gln missense NM_001408492.1:c.1979G>A NP_001395421.1:p.Arg660Gln missense NM_001408493.1:c.1979G>A NP_001395422.1:p.Arg660Gln missense NM_001408494.1:c.1955G>A NP_001395423.1:p.Arg652Gln missense NM_001408495.1:c.1949G>A NP_001395424.1:p.Arg650Gln missense NM_001408496.1:c.1931G>A NP_001395425.1:p.Arg644Gln missense NM_001408497.1:c.1931G>A NP_001395426.1:p.Arg644Gln missense NM_001408498.1:c.1931G>A NP_001395427.1:p.Arg644Gln missense NM_001408499.1:c.1931G>A NP_001395428.1:p.Arg644Gln missense NM_001408500.1:c.1931G>A NP_001395429.1:p.Arg644Gln missense NM_001408501.1:c.1931G>A NP_001395430.1:p.Arg644Gln missense NM_001408502.1:c.1928G>A NP_001395431.1:p.Arg643Gln missense NM_001408503.1:c.1928G>A NP_001395432.1:p.Arg643Gln missense NM_001408504.1:c.1928G>A NP_001395433.1:p.Arg643Gln missense NM_001408505.1:c.1925G>A NP_001395434.1:p.Arg642Gln missense NM_001408506.1:c.1868G>A NP_001395435.1:p.Arg623Gln missense NM_001408507.1:c.1865G>A NP_001395436.1:p.Arg622Gln missense NM_001408508.1:c.1856G>A NP_001395437.1:p.Arg619Gln missense NM_001408509.1:c.1853G>A NP_001395438.1:p.Arg618Gln missense NM_001408510.1:c.1814G>A NP_001395439.1:p.Arg605Gln missense NM_001408511.1:c.1811G>A NP_001395440.1:p.Arg604Gln missense NM_001408512.1:c.1691G>A NP_001395441.1:p.Arg564Gln missense NM_001408513.1:c.1664G>A NP_001395442.1:p.Arg555Gln missense NM_001408514.1:c.1268G>A NP_001395443.1:p.Arg423Gln missense NM_007297.4:c.5363G>A NP_009228.2:p.Arg1788Gln missense NM_007298.4:c.2192G>A NP_009229.2:p.Arg731Gln missense NM_007299.4:c.*18G>A 3 prime UTR NM_007300.4:c.5567G>A NP_009231.2:p.Arg1856Gln missense NM_007304.2:c.2192G>A NP_009235.2:p.Arg731Gln missense NR_027676.2:n.5681G>A non-coding transcript variant NC_000017.11:g.43045766C>T NC_000017.10:g.41197783C>T NG_005905.2:g.172218G>A LRG_292:g.172218G>A LRG_292t1:c.5504G>A LRG_292p1:p.Arg1835Gln U14680.1:n.5623G>A - Protein change
- R1835Q, R731Q, R1788Q, R1856Q, R1707Q, R1751Q, R1763Q, R1787Q, R1793Q, R1808Q, R1831Q, R1833Q, R1834Q, R555Q, R604Q, R622Q, R643Q, R644Q, R650Q, R664Q, R684Q, R690Q, R692Q, R705Q, R730Q, R753Q, R966Q, R1538Q, R1765Q, R1766Q, R1768Q, R1794Q, R1807Q, R1809Q, R1855Q, R423Q, R564Q, R652Q, R662Q, R687Q, R754Q, R967Q, R1539Q, R1681Q, R1706Q, R1708Q, R1722Q, R1723Q, R1724Q, R1747Q, R1767Q, R1786Q, R1815Q, R1832Q, R1857Q, R623Q, R642Q, R683Q, R685Q, R691Q, R693Q, R706Q, R728Q, R732Q, R1666Q, R1745Q, R1746Q, R1764Q, R1791Q, R1792Q, R1816Q, R1830Q, R605Q, R618Q, R619Q, R660Q, R661Q, R665Q, R689Q, R707Q, R729Q
- Other names
- 5623G>A
- Canonical SPDI
- NC_000017.11:43045765:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- function_uncertain_variant Sequence Ontology [SO:0002220]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5504G>A, a MISSENSE variant, produced a function score of -0.91, corresponding to a functional classification of INTERMEDIATE. 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) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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 |
12880 | 14665 |
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. |
---|---|---|---|---|
Likely benign (1) |
criteria provided, single submitter
|
Jan 25, 2024 | RCV000049023.20 | |
Uncertain significance (6) |
criteria provided, multiple submitters, no conflicts
|
Sep 27, 2023 | RCV000112685.14 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000120265.17 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 27, 2023 | RCV000130437.21 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Nov 1, 2015 | RCV000240743.9 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Dec 20, 2018 | RCV000588102.10 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Nov 01, 2015)
|
criteria provided, single submitter
Method: research
|
Breast neoplasm
Affected status: yes
Allele origin:
germline
|
Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University
Additional submitter:
Asia and Emerging Markets iMed, AstraZeneca
Accession: SCV000265893.1
First in ClinVar: Sep 14, 2016 Last updated: Sep 14, 2016 |
Number of individuals with the variant: 1
Geographic origin: China
|
|
Uncertain significance
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002760916.3
First in ClinVar: Dec 17, 2022 Last updated: Aug 18, 2023 |
|
|
Uncertain significance
(Sep 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212751.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Uncertain significance
(Jan 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683328.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with glutamine at codon 1835 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces arginine with glutamine at codon 1835 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have shown the mutant protein to be partially functional in a homology-directed DNA repair assay (PMID: 26689913) and in a haploid cell proliferation assay (PMID: 30209399) and show enhanced transactivation activity (PMID: 28781887, 30458859). This variant has been reported in individuals affected with breast cancer (PMID: 17972177, 27257965, 35402282), ovarian cancer (PMID: 18627636, 24504028) and pancreatic cancer (PMID: 32980694 ). This variant has also been observed in a healthy control individual (PMID: 27403073). This variant has been identified in 9/282720 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
Likely benign
(Jan 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000077036.12
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
|
|
Uncertain significance
(Mar 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000786203.2
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
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Uncertain significance
(Dec 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000566085.4
First in ClinVar: Jun 09, 2014 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted BRCA1 c.5504G>A at the cDNA level, p.Arg1835Gln (R1835Q) at the protein level, and results in the change of an Arginine to … (more)
This variant is denoted BRCA1 c.5504G>A at the cDNA level, p.Arg1835Gln (R1835Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). Using alternate nomenclature, this variant has been previously published as BRCA1 5623G>A. This variant was observed in individuals with personal and/or family histories of breast and/or ovarian cancer, as well as in at least one individual with gastric cancer (Purnomosari 2007, Thirthagiri 2008, Cunningham 2014, Lu 2015). Functional assays demonstrated that this variant displayed partial or intermediate deficiency in homology-directed repair activity, but retained normal transactivation function comparable to wild-type (Lu 2015, Woods 2016, Langerud 2018, Findlay 2018). BRCA1 Arg1835Gln was also identified in 1/46 healthy African-European individuals undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of this individual may not be significant. BRCA1 Arg1835Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the BRCT2 domain as well as a region known to interact with multiple proteins (Paul 2014, UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Arg1835Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
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Uncertain significance
(Sep 06, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699268.2
First in ClinVar: Mar 17, 2018 Last updated: Nov 05, 2022 |
Comment:
Variant summary: BRCA1 c.5504G>A (p.Arg1835Gln) results in a conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of … (more)
Variant summary: BRCA1 c.5504G>A (p.Arg1835Gln) results in a conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251424 control chromosomes.c.5504G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer from diverse ethnic populations without strong evidence for causality (eg. Purnomosari_2007, Thirthagiri_2008, Cunningham_2014, Zhong_2016, Zidan_2017, etc). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Functional studies demonstrated that the variant protein displayed partial or intermediate deficiency in homology-directed repair (HDR) activity with a preserved transactivation function (Findlay_2018, Lu_2015, Woods_2016). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Five classified the variant as VUS while one classified as likley benign. Based on the evidence outlined above, the variant was classified as VUS. (less)
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Uncertain Significance
(Apr 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004817535.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces arginine with glutamine at codon 1835 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces arginine with glutamine at codon 1835 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have shown the mutant protein to be partially functional in a homology-directed DNA repair assay (PMID: 26689913) and in a haploid cell proliferation assay (PMID: 30209399) and show enhanced transactivation activity (PMID: 28781887, 30458859). This variant has been reported in individuals affected with breast cancer (PMID: 17972177, 27257965, 35402282), ovarian cancer (PMID: 18627636, 24504028) and pancreatic cancer (PMID: 32980694 ). This variant has also been observed in a healthy control individual (PMID: 27403073). This variant has been identified in 9/282720 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 2
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Uncertain significance
(Dec 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000185301.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.R1835Q variant (also known as c.5504G>A), located in coding exon 22 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.R1835Q variant (also known as c.5504G>A), located in coding exon 22 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5504. The arginine at codon 1835 is replaced by glutamine, an amino acid with highly similar properties. This alteration was identified in individuals from high-risk breast/ovarian cancer families from diverse ethnic backgrounds (Zidan J et al. Breast Cancer Res. Treat. 2017 Dec;166:881-885; Liang Y et al. Med. Sci. Monit. 2018 Apr;24:2465-2475; Bhaskaran SP et al. Int. J. Cancer. 2019 Aug;145:962-973; Purnomosari D et al. Breast Cancer Res. Treat. 2007 Dec;106:297-304; Thirthagiri E et al. Breast Cancer Res. 2008 Jul;10:R59), but also in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS ONE. 2014 Apr;9:e94554). This alteration was identified in a male patient with stomach cancer at age 48, and a functional comparison showed that this alteration displayed less than 70% homology-directed repair (HDR) function in comparison to wild type BRCA1 (Lu C et al. Nat Commun. 2015 Dec;6:10086). In a high throughput genome editing haploid cell survival assay, this nucleotide substitution had intermediate activity (Findlay GM et al. Nature. 2018 10;562:217-222). In addition, two different transactivation assays demonstrated that this alteration does not significantly disrupt transactivation activity (Langerud J et al. Hum. Genomics. 2018 11;12:51; Fernández-Lopez JC et al. Hum. Genomics. 2019 01;13:3). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited and conflicting at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Sep 18, 2010)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145553.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 2
Ethnicity/Population group: Malay
Geographic origin: Malaysia
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Uncertain significance
(Jul 06, 2009)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000297622.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
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Uncertain significance
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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not specified
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587515.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084417.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001237593.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
INTERMEDIATE:-0.906347441715577
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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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
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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. |
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function_uncertain_variant
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237593.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5504G>A, a MISSENSE variant, produced a function score of -0.91, corresponding to a functional classification of INTERMEDIATE. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5504G>A, a MISSENSE variant, produced a function score of -0.91, corresponding to a functional classification of INTERMEDIATE. 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)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Rates of Variants of Uncertain Significance Among Patients With Breast Cancer Undergoing Genetic Testing: Regional Perspectives. | Abdel-Razeq H | Frontiers in oncology | 2022 | PMID: 35402282 |
BRCA1 Norway: comparison of classification for BRCA1 germline variants detected in families with suspected hereditary breast and ovarian cancer between different laboratories. | Hovland HN | Familial cancer | 2022 | PMID: 34981296 |
Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes. | Mizukami K | EBioMedicine | 2020 | PMID: 32980694 |
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 |
Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population. | Fernández-Lopez JC | Human genomics | 2019 | PMID: 30630528 |
Trans-activation-based risk assessment of BRCA1 BRCT variants with unknown clinical significance. | Langerud J | Human genomics | 2018 | PMID: 30458859 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Prevalence and Spectrum of BRCA1/2 Germline Mutations in Women with Breast Cancer in China Based on Next-Generation Sequencing. | Liang Y | Medical science monitor : international medical journal of experimental and clinical research | 2018 | PMID: 29681614 |
Inherited predisposition to breast and ovarian cancer in non-Jewish populations in Israel. | Zidan J | Breast cancer research and treatment | 2017 | PMID: 28828701 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
BRCA1 and BRCA2 sequence variations detected with next-generation sequencing in patients with premature ovarian insufficiency. | Yılmaz NK | Journal of the Turkish German Gynecological Association | 2016 | PMID: 27403073 |
Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients. | Zhong X | PloS one | 2016 | PMID: 27257965 |
Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
Probing structure-function relationships in missense variants in the carboxy-terminal region of BRCA1. | Carvalho RS | PloS one | 2014 | PMID: 24845084 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
A computational method to classify variants of uncertain significance using functional assay data with application to BRCA1. | Iversen ES Jr | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2011 | PMID: 21447777 |
Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. | Thirthagiri E | Breast cancer research : BCR | 2008 | PMID: 18627636 |
BRCA1 and BRCA2 germline mutation analysis in the Indonesian population. | Purnomosari D | Breast cancer research and treatment | 2007 | PMID: 17972177 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs273902776 ...
HelpRecord last updated May 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.