ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5509T>C (p.Trp1837Arg)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5509T>C (p.Trp1837Arg)
Variation ID: 37679 Accession: VCV000037679.42
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045761 (GRCh38) [ NCBI UCSC ] 17: 41197778 (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 Sep 16, 2024 Jun 18, 2019 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_007294.4:c.5509T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Trp1837Arg missense NM_001407571.1:c.5296T>C NP_001394500.1:p.Trp1766Arg missense NM_001407581.1:c.5575T>C NP_001394510.1:p.Trp1859Arg missense NM_001407582.1:c.5575T>C NP_001394511.1:p.Trp1859Arg missense NM_001407583.1:c.5572T>C NP_001394512.1:p.Trp1858Arg missense NM_001407585.1:c.5572T>C NP_001394514.1:p.Trp1858Arg missense NM_001407587.1:c.5572T>C NP_001394516.1:p.Trp1858Arg missense NM_001407590.1:c.5569T>C NP_001394519.1:p.Trp1857Arg missense NM_001407591.1:c.5569T>C NP_001394520.1:p.Trp1857Arg missense NM_001407593.1:c.5509T>C NP_001394522.1:p.Trp1837Arg missense NM_001407594.1:c.5509T>C NP_001394523.1:p.Trp1837Arg missense NM_001407596.1:c.5509T>C NP_001394525.1:p.Trp1837Arg missense NM_001407597.1:c.5509T>C NP_001394526.1:p.Trp1837Arg missense NM_001407598.1:c.5509T>C NP_001394527.1:p.Trp1837Arg missense NM_001407602.1:c.5509T>C NP_001394531.1:p.Trp1837Arg missense NM_001407603.1:c.5509T>C NP_001394532.1:p.Trp1837Arg missense NM_001407605.1:c.5509T>C NP_001394534.1:p.Trp1837Arg missense NM_001407610.1:c.5506T>C NP_001394539.1:p.Trp1836Arg missense NM_001407611.1:c.5506T>C NP_001394540.1:p.Trp1836Arg missense NM_001407612.1:c.5506T>C NP_001394541.1:p.Trp1836Arg missense NM_001407613.1:c.5506T>C NP_001394542.1:p.Trp1836Arg missense NM_001407614.1:c.5506T>C NP_001394543.1:p.Trp1836Arg missense NM_001407615.1:c.5506T>C NP_001394544.1:p.Trp1836Arg missense NM_001407616.1:c.5506T>C NP_001394545.1:p.Trp1836Arg missense NM_001407617.1:c.5506T>C NP_001394546.1:p.Trp1836Arg missense NM_001407618.1:c.5506T>C NP_001394547.1:p.Trp1836Arg missense NM_001407619.1:c.5506T>C NP_001394548.1:p.Trp1836Arg missense NM_001407620.1:c.5506T>C NP_001394549.1:p.Trp1836Arg missense NM_001407621.1:c.5506T>C NP_001394550.1:p.Trp1836Arg missense NM_001407622.1:c.5506T>C NP_001394551.1:p.Trp1836Arg missense NM_001407623.1:c.5506T>C NP_001394552.1:p.Trp1836Arg missense NM_001407624.1:c.5506T>C NP_001394553.1:p.Trp1836Arg missense NM_001407625.1:c.5506T>C NP_001394554.1:p.Trp1836Arg missense NM_001407626.1:c.5506T>C NP_001394555.1:p.Trp1836Arg missense NM_001407627.1:c.5503T>C NP_001394556.1:p.Trp1835Arg missense NM_001407628.1:c.5503T>C NP_001394557.1:p.Trp1835Arg missense NM_001407629.1:c.5503T>C NP_001394558.1:p.Trp1835Arg missense NM_001407630.1:c.5503T>C NP_001394559.1:p.Trp1835Arg missense NM_001407631.1:c.5503T>C NP_001394560.1:p.Trp1835Arg missense NM_001407632.1:c.5503T>C NP_001394561.1:p.Trp1835Arg missense NM_001407633.1:c.5503T>C NP_001394562.1:p.Trp1835Arg missense NM_001407634.1:c.5503T>C NP_001394563.1:p.Trp1835Arg missense NM_001407635.1:c.5503T>C NP_001394564.1:p.Trp1835Arg missense NM_001407636.1:c.5503T>C NP_001394565.1:p.Trp1835Arg missense NM_001407637.1:c.5503T>C NP_001394566.1:p.Trp1835Arg missense NM_001407638.1:c.5503T>C NP_001394567.1:p.Trp1835Arg missense NM_001407639.1:c.5503T>C NP_001394568.1:p.Trp1835Arg missense NM_001407640.1:c.5503T>C NP_001394569.1:p.Trp1835Arg missense NM_001407641.1:c.5503T>C NP_001394570.1:p.Trp1835Arg missense NM_001407642.1:c.5503T>C NP_001394571.1:p.Trp1835Arg missense NM_001407644.1:c.5500T>C NP_001394573.1:p.Trp1834Arg missense NM_001407645.1:c.5500T>C NP_001394574.1:p.Trp1834Arg missense NM_001407646.1:c.5497T>C NP_001394575.1:p.Trp1833Arg missense NM_001407647.1:c.5494T>C NP_001394576.1:p.Trp1832Arg missense NM_001407648.1:c.5452T>C NP_001394577.1:p.Trp1818Arg missense NM_001407649.1:c.5449T>C NP_001394578.1:p.Trp1817Arg missense NM_001407652.1:c.5431T>C NP_001394581.1:p.Trp1811Arg missense NM_001407653.1:c.5431T>C NP_001394582.1:p.Trp1811Arg missense NM_001407654.1:c.5431T>C NP_001394583.1:p.Trp1811Arg missense NM_001407655.1:c.5431T>C NP_001394584.1:p.Trp1811Arg missense NM_001407656.1:c.5428T>C NP_001394585.1:p.Trp1810Arg missense NM_001407657.1:c.5428T>C NP_001394586.1:p.Trp1810Arg missense NM_001407658.1:c.5428T>C NP_001394587.1:p.Trp1810Arg missense NM_001407659.1:c.5425T>C NP_001394588.1:p.Trp1809Arg missense NM_001407660.1:c.5425T>C NP_001394589.1:p.Trp1809Arg missense NM_001407661.1:c.5425T>C NP_001394590.1:p.Trp1809Arg missense NM_001407662.1:c.5425T>C NP_001394591.1:p.Trp1809Arg missense NM_001407663.1:c.5425T>C NP_001394592.1:p.Trp1809Arg missense NM_001407664.1:c.5386T>C NP_001394593.1:p.Trp1796Arg missense NM_001407665.1:c.5386T>C NP_001394594.1:p.Trp1796Arg missense NM_001407666.1:c.5386T>C NP_001394595.1:p.Trp1796Arg missense NM_001407667.1:c.5386T>C NP_001394596.1:p.Trp1796Arg missense NM_001407668.1:c.5386T>C NP_001394597.1:p.Trp1796Arg missense NM_001407669.1:c.5386T>C NP_001394598.1:p.Trp1796Arg missense NM_001407670.1:c.5383T>C NP_001394599.1:p.Trp1795Arg missense NM_001407671.1:c.5383T>C NP_001394600.1:p.Trp1795Arg missense NM_001407672.1:c.5383T>C NP_001394601.1:p.Trp1795Arg missense NM_001407673.1:c.5383T>C NP_001394602.1:p.Trp1795Arg missense NM_001407674.1:c.5383T>C NP_001394603.1:p.Trp1795Arg missense NM_001407675.1:c.5383T>C NP_001394604.1:p.Trp1795Arg missense NM_001407676.1:c.5383T>C NP_001394605.1:p.Trp1795Arg missense NM_001407677.1:c.5383T>C NP_001394606.1:p.Trp1795Arg missense NM_001407678.1:c.5383T>C NP_001394607.1:p.Trp1795Arg missense NM_001407679.1:c.5383T>C NP_001394608.1:p.Trp1795Arg missense NM_001407680.1:c.5383T>C NP_001394609.1:p.Trp1795Arg missense NM_001407681.1:c.5380T>C NP_001394610.1:p.Trp1794Arg missense NM_001407682.1:c.5380T>C NP_001394611.1:p.Trp1794Arg missense NM_001407683.1:c.5380T>C NP_001394612.1:p.Trp1794Arg missense NM_001407684.1:c.5380T>C NP_001394613.1:p.Trp1794Arg missense NM_001407685.1:c.5380T>C NP_001394614.1:p.Trp1794Arg missense NM_001407686.1:c.5380T>C NP_001394615.1:p.Trp1794Arg missense NM_001407687.1:c.5380T>C NP_001394616.1:p.Trp1794Arg missense NM_001407688.1:c.5380T>C NP_001394617.1:p.Trp1794Arg missense NM_001407689.1:c.5380T>C NP_001394618.1:p.Trp1794Arg missense NM_001407690.1:c.5377T>C NP_001394619.1:p.Trp1793Arg missense NM_001407691.1:c.5377T>C NP_001394620.1:p.Trp1793Arg missense NM_001407692.1:c.5368T>C NP_001394621.1:p.Trp1790Arg missense NM_001407694.1:c.5368T>C NP_001394623.1:p.Trp1790Arg missense NM_001407695.1:c.5368T>C NP_001394624.1:p.Trp1790Arg missense NM_001407696.1:c.5368T>C NP_001394625.1:p.Trp1790Arg missense NM_001407697.1:c.5368T>C NP_001394626.1:p.Trp1790Arg missense NM_001407698.1:c.5368T>C NP_001394627.1:p.Trp1790Arg missense NM_001407724.1:c.5368T>C NP_001394653.1:p.Trp1790Arg missense NM_001407725.1:c.5368T>C NP_001394654.1:p.Trp1790Arg missense NM_001407726.1:c.5368T>C NP_001394655.1:p.Trp1790Arg missense NM_001407727.1:c.5368T>C NP_001394656.1:p.Trp1790Arg missense NM_001407728.1:c.5368T>C NP_001394657.1:p.Trp1790Arg missense NM_001407729.1:c.5368T>C NP_001394658.1:p.Trp1790Arg missense NM_001407730.1:c.5368T>C NP_001394659.1:p.Trp1790Arg missense NM_001407731.1:c.5368T>C NP_001394660.1:p.Trp1790Arg missense NM_001407732.1:c.5365T>C NP_001394661.1:p.Trp1789Arg missense NM_001407733.1:c.5365T>C NP_001394662.1:p.Trp1789Arg missense NM_001407734.1:c.5365T>C NP_001394663.1:p.Trp1789Arg missense NM_001407735.1:c.5365T>C NP_001394664.1:p.Trp1789Arg missense NM_001407736.1:c.5365T>C NP_001394665.1:p.Trp1789Arg missense NM_001407737.1:c.5365T>C NP_001394666.1:p.Trp1789Arg missense NM_001407738.1:c.5365T>C NP_001394667.1:p.Trp1789Arg missense NM_001407739.1:c.5365T>C NP_001394668.1:p.Trp1789Arg missense NM_001407740.1:c.5365T>C NP_001394669.1:p.Trp1789Arg missense NM_001407741.1:c.5365T>C NP_001394670.1:p.Trp1789Arg missense NM_001407742.1:c.5365T>C NP_001394671.1:p.Trp1789Arg missense NM_001407743.1:c.5365T>C NP_001394672.1:p.Trp1789Arg missense NM_001407744.1:c.5365T>C NP_001394673.1:p.Trp1789Arg missense NM_001407745.1:c.5365T>C NP_001394674.1:p.Trp1789Arg missense NM_001407746.1:c.5365T>C NP_001394675.1:p.Trp1789Arg missense NM_001407747.1:c.5365T>C NP_001394676.1:p.Trp1789Arg missense NM_001407748.1:c.5365T>C NP_001394677.1:p.Trp1789Arg missense NM_001407749.1:c.5365T>C NP_001394678.1:p.Trp1789Arg missense NM_001407750.1:c.5365T>C NP_001394679.1:p.Trp1789Arg missense NM_001407751.1:c.5365T>C NP_001394680.1:p.Trp1789Arg missense NM_001407752.1:c.5365T>C NP_001394681.1:p.Trp1789Arg missense NM_001407838.1:c.5362T>C NP_001394767.1:p.Trp1788Arg missense NM_001407839.1:c.5362T>C NP_001394768.1:p.Trp1788Arg missense NM_001407841.1:c.5362T>C NP_001394770.1:p.Trp1788Arg missense NM_001407842.1:c.5362T>C NP_001394771.1:p.Trp1788Arg missense NM_001407843.1:c.5362T>C NP_001394772.1:p.Trp1788Arg missense NM_001407844.1:c.5362T>C NP_001394773.1:p.Trp1788Arg missense NM_001407845.1:c.5362T>C NP_001394774.1:p.Trp1788Arg missense NM_001407846.1:c.5362T>C NP_001394775.1:p.Trp1788Arg missense NM_001407847.1:c.5362T>C NP_001394776.1:p.Trp1788Arg missense NM_001407848.1:c.5362T>C NP_001394777.1:p.Trp1788Arg missense NM_001407849.1:c.5362T>C NP_001394778.1:p.Trp1788Arg missense NM_001407850.1:c.5362T>C NP_001394779.1:p.Trp1788Arg missense NM_001407851.1:c.5362T>C NP_001394780.1:p.Trp1788Arg missense NM_001407852.1:c.5362T>C NP_001394781.1:p.Trp1788Arg missense NM_001407853.1:c.5362T>C NP_001394782.1:p.Trp1788Arg missense NM_001407854.1:c.*23T>C NM_001407858.1:c.*23T>C NM_001407859.1:c.*23T>C NM_001407860.1:c.*23T>C NM_001407861.1:c.*23T>C NM_001407862.1:c.5308T>C NP_001394791.1:p.Trp1770Arg missense NM_001407863.1:c.5305T>C NP_001394792.1:p.Trp1769Arg missense NM_001407874.1:c.5302T>C NP_001394803.1:p.Trp1768Arg missense NM_001407875.1:c.5302T>C NP_001394804.1:p.Trp1768Arg missense NM_001407879.1:c.5299T>C NP_001394808.1:p.Trp1767Arg missense NM_001407881.1:c.5299T>C NP_001394810.1:p.Trp1767Arg missense NM_001407882.1:c.5299T>C NP_001394811.1:p.Trp1767Arg missense NM_001407884.1:c.5299T>C NP_001394813.1:p.Trp1767Arg missense NM_001407885.1:c.5299T>C NP_001394814.1:p.Trp1767Arg missense NM_001407886.1:c.5299T>C NP_001394815.1:p.Trp1767Arg missense NM_001407887.1:c.5299T>C NP_001394816.1:p.Trp1767Arg missense NM_001407889.1:c.5299T>C NP_001394818.1:p.Trp1767Arg missense NM_001407894.1:c.5296T>C NP_001394823.1:p.Trp1766Arg missense NM_001407895.1:c.5296T>C NP_001394824.1:p.Trp1766Arg missense NM_001407896.1:c.5296T>C NP_001394825.1:p.Trp1766Arg missense NM_001407897.1:c.5296T>C NP_001394826.1:p.Trp1766Arg missense NM_001407898.1:c.5296T>C NP_001394827.1:p.Trp1766Arg missense NM_001407899.1:c.5296T>C NP_001394828.1:p.Trp1766Arg missense NM_001407900.1:c.5296T>C NP_001394829.1:p.Trp1766Arg missense NM_001407902.1:c.5296T>C NP_001394831.1:p.Trp1766Arg missense NM_001407904.1:c.5296T>C NP_001394833.1:p.Trp1766Arg missense NM_001407906.1:c.5296T>C NP_001394835.1:p.Trp1766Arg missense NM_001407907.1:c.5296T>C NP_001394836.1:p.Trp1766Arg missense NM_001407908.1:c.5296T>C NP_001394837.1:p.Trp1766Arg missense NM_001407909.1:c.5296T>C NP_001394838.1:p.Trp1766Arg missense NM_001407910.1:c.5296T>C NP_001394839.1:p.Trp1766Arg missense NM_001407915.1:c.5293T>C NP_001394844.1:p.Trp1765Arg missense NM_001407916.1:c.5293T>C NP_001394845.1:p.Trp1765Arg missense NM_001407917.1:c.5293T>C NP_001394846.1:p.Trp1765Arg missense NM_001407918.1:c.5293T>C NP_001394847.1:p.Trp1765Arg missense NM_001407919.1:c.5257T>C NP_001394848.1:p.Trp1753Arg missense NM_001407920.1:c.5245T>C NP_001394849.1:p.Trp1749Arg missense NM_001407921.1:c.5245T>C NP_001394850.1:p.Trp1749Arg missense NM_001407922.1:c.5245T>C NP_001394851.1:p.Trp1749Arg missense NM_001407923.1:c.5245T>C NP_001394852.1:p.Trp1749Arg missense NM_001407924.1:c.5245T>C NP_001394853.1:p.Trp1749Arg missense NM_001407925.1:c.5245T>C NP_001394854.1:p.Trp1749Arg missense NM_001407926.1:c.5245T>C NP_001394855.1:p.Trp1749Arg missense NM_001407927.1:c.5242T>C NP_001394856.1:p.Trp1748Arg missense NM_001407928.1:c.5242T>C NP_001394857.1:p.Trp1748Arg missense NM_001407929.1:c.5242T>C NP_001394858.1:p.Trp1748Arg missense NM_001407930.1:c.5242T>C NP_001394859.1:p.Trp1748Arg missense NM_001407931.1:c.5242T>C NP_001394860.1:p.Trp1748Arg missense NM_001407932.1:c.5242T>C NP_001394861.1:p.Trp1748Arg missense NM_001407933.1:c.5242T>C NP_001394862.1:p.Trp1748Arg missense NM_001407934.1:c.5239T>C NP_001394863.1:p.Trp1747Arg missense NM_001407935.1:c.5239T>C NP_001394864.1:p.Trp1747Arg missense NM_001407936.1:c.5239T>C NP_001394865.1:p.Trp1747Arg missense NM_001407937.1:c.*23T>C NM_001407938.1:c.*23T>C NM_001407939.1:c.*23T>C NM_001407940.1:c.*23T>C NM_001407941.1:c.*23T>C NM_001407942.1:c.*23T>C NM_001407943.1:c.*23T>C NM_001407944.1:c.*23T>C NM_001407945.1:c.*23T>C NM_001407946.1:c.5176T>C NP_001394875.1:p.Trp1726Arg missense NM_001407947.1:c.5176T>C NP_001394876.1:p.Trp1726Arg missense NM_001407948.1:c.5176T>C NP_001394877.1:p.Trp1726Arg missense NM_001407949.1:c.5176T>C NP_001394878.1:p.Trp1726Arg missense NM_001407950.1:c.5173T>C NP_001394879.1:p.Trp1725Arg missense NM_001407951.1:c.5173T>C NP_001394880.1:p.Trp1725Arg missense NM_001407952.1:c.5173T>C NP_001394881.1:p.Trp1725Arg missense NM_001407953.1:c.5173T>C NP_001394882.1:p.Trp1725Arg missense NM_001407954.1:c.5173T>C NP_001394883.1:p.Trp1725Arg missense NM_001407955.1:c.5173T>C NP_001394884.1:p.Trp1725Arg missense NM_001407956.1:c.5170T>C NP_001394885.1:p.Trp1724Arg missense NM_001407957.1:c.5170T>C NP_001394886.1:p.Trp1724Arg missense NM_001407958.1:c.5170T>C NP_001394887.1:p.Trp1724Arg missense NM_001407959.1:c.5128T>C NP_001394888.1:p.Trp1710Arg missense NM_001407960.1:c.5125T>C NP_001394889.1:p.Trp1709Arg missense NM_001407962.1:c.5125T>C NP_001394891.1:p.Trp1709Arg missense NM_001407963.1:c.5122T>C NP_001394892.1:p.Trp1708Arg missense NM_001407964.1:c.5047T>C NP_001394893.1:p.Trp1683Arg missense NM_001407965.1:c.5002T>C NP_001394894.1:p.Trp1668Arg missense NM_001407966.1:c.4621T>C NP_001394895.1:p.Trp1541Arg missense NM_001407967.1:c.4618T>C NP_001394896.1:p.Trp1540Arg missense NM_001407968.1:c.2905T>C NP_001394897.1:p.Trp969Arg missense NM_001407969.1:c.2902T>C NP_001394898.1:p.Trp968Arg missense NM_001407970.1:c.2266T>C NP_001394899.1:p.Trp756Arg missense NM_001407971.1:c.2266T>C NP_001394900.1:p.Trp756Arg missense NM_001407972.1:c.2263T>C NP_001394901.1:p.Trp755Arg missense NM_001407973.1:c.2200T>C NP_001394902.1:p.Trp734Arg missense NM_001407974.1:c.2200T>C NP_001394903.1:p.Trp734Arg missense NM_001407975.1:c.2200T>C NP_001394904.1:p.Trp734Arg missense NM_001407976.1:c.2200T>C NP_001394905.1:p.Trp734Arg missense NM_001407977.1:c.2200T>C NP_001394906.1:p.Trp734Arg missense NM_001407978.1:c.2200T>C NP_001394907.1:p.Trp734Arg missense NM_001407979.1:c.2197T>C NP_001394908.1:p.Trp733Arg missense NM_001407980.1:c.2197T>C NP_001394909.1:p.Trp733Arg missense NM_001407981.1:c.2197T>C NP_001394910.1:p.Trp733Arg missense NM_001407982.1:c.2197T>C NP_001394911.1:p.Trp733Arg missense NM_001407983.1:c.2197T>C NP_001394912.1:p.Trp733Arg missense NM_001407984.1:c.2197T>C NP_001394913.1:p.Trp733Arg missense NM_001407985.1:c.2197T>C NP_001394914.1:p.Trp733Arg missense NM_001407986.1:c.2197T>C NP_001394915.1:p.Trp733Arg missense NM_001407990.1:c.2197T>C NP_001394919.1:p.Trp733Arg missense NM_001407991.1:c.2197T>C NP_001394920.1:p.Trp733Arg missense NM_001407992.1:c.2197T>C NP_001394921.1:p.Trp733Arg missense NM_001407993.1:c.2197T>C NP_001394922.1:p.Trp733Arg missense NM_001408392.1:c.2194T>C NP_001395321.1:p.Trp732Arg missense NM_001408396.1:c.2194T>C NP_001395325.1:p.Trp732Arg missense NM_001408397.1:c.2194T>C NP_001395326.1:p.Trp732Arg missense NM_001408398.1:c.2194T>C NP_001395327.1:p.Trp732Arg missense NM_001408399.1:c.2194T>C NP_001395328.1:p.Trp732Arg missense NM_001408400.1:c.2194T>C NP_001395329.1:p.Trp732Arg missense NM_001408401.1:c.2194T>C NP_001395330.1:p.Trp732Arg missense NM_001408402.1:c.2194T>C NP_001395331.1:p.Trp732Arg missense NM_001408403.1:c.2194T>C NP_001395332.1:p.Trp732Arg missense NM_001408404.1:c.2194T>C NP_001395333.1:p.Trp732Arg missense NM_001408406.1:c.2191T>C NP_001395335.1:p.Trp731Arg missense NM_001408407.1:c.2191T>C NP_001395336.1:p.Trp731Arg missense NM_001408408.1:c.2191T>C NP_001395337.1:p.Trp731Arg missense NM_001408409.1:c.2188T>C NP_001395338.1:p.Trp730Arg missense NM_001408410.1:c.2125T>C NP_001395339.1:p.Trp709Arg missense NM_001408411.1:c.2122T>C NP_001395340.1:p.Trp708Arg missense NM_001408412.1:c.2119T>C NP_001395341.1:p.Trp707Arg missense NM_001408413.1:c.2119T>C NP_001395342.1:p.Trp707Arg missense NM_001408414.1:c.2119T>C NP_001395343.1:p.Trp707Arg missense NM_001408415.1:c.2119T>C NP_001395344.1:p.Trp707Arg missense NM_001408416.1:c.2119T>C NP_001395345.1:p.Trp707Arg missense NM_001408418.1:c.2083T>C NP_001395347.1:p.Trp695Arg missense NM_001408419.1:c.2083T>C NP_001395348.1:p.Trp695Arg missense NM_001408420.1:c.2083T>C NP_001395349.1:p.Trp695Arg missense NM_001408421.1:c.2080T>C NP_001395350.1:p.Trp694Arg missense NM_001408422.1:c.2080T>C NP_001395351.1:p.Trp694Arg missense NM_001408423.1:c.2080T>C NP_001395352.1:p.Trp694Arg missense NM_001408424.1:c.2080T>C NP_001395353.1:p.Trp694Arg missense NM_001408425.1:c.2077T>C NP_001395354.1:p.Trp693Arg missense NM_001408426.1:c.2077T>C NP_001395355.1:p.Trp693Arg missense NM_001408427.1:c.2077T>C NP_001395356.1:p.Trp693Arg missense NM_001408428.1:c.2077T>C NP_001395357.1:p.Trp693Arg missense NM_001408429.1:c.2077T>C NP_001395358.1:p.Trp693Arg missense NM_001408430.1:c.2077T>C NP_001395359.1:p.Trp693Arg missense NM_001408431.1:c.2077T>C NP_001395360.1:p.Trp693Arg missense NM_001408432.1:c.2074T>C NP_001395361.1:p.Trp692Arg missense NM_001408433.1:c.2074T>C NP_001395362.1:p.Trp692Arg missense NM_001408434.1:c.2074T>C NP_001395363.1:p.Trp692Arg missense NM_001408435.1:c.2074T>C NP_001395364.1:p.Trp692Arg missense NM_001408436.1:c.2074T>C NP_001395365.1:p.Trp692Arg missense NM_001408437.1:c.2074T>C NP_001395366.1:p.Trp692Arg missense NM_001408438.1:c.2074T>C NP_001395367.1:p.Trp692Arg missense NM_001408439.1:c.2074T>C NP_001395368.1:p.Trp692Arg missense NM_001408440.1:c.2074T>C NP_001395369.1:p.Trp692Arg missense NM_001408441.1:c.2074T>C NP_001395370.1:p.Trp692Arg missense NM_001408442.1:c.2074T>C NP_001395371.1:p.Trp692Arg missense NM_001408443.1:c.2074T>C NP_001395372.1:p.Trp692Arg missense NM_001408444.1:c.2074T>C NP_001395373.1:p.Trp692Arg missense NM_001408445.1:c.2071T>C NP_001395374.1:p.Trp691Arg missense NM_001408446.1:c.2071T>C NP_001395375.1:p.Trp691Arg missense NM_001408447.1:c.2071T>C NP_001395376.1:p.Trp691Arg missense NM_001408448.1:c.2071T>C NP_001395377.1:p.Trp691Arg missense NM_001408450.1:c.2071T>C NP_001395379.1:p.Trp691Arg missense NM_001408451.1:c.2065T>C NP_001395380.1:p.Trp689Arg missense NM_001408452.1:c.2059T>C NP_001395381.1:p.Trp687Arg missense NM_001408453.1:c.2059T>C NP_001395382.1:p.Trp687Arg missense NM_001408454.1:c.2059T>C NP_001395383.1:p.Trp687Arg missense NM_001408455.1:c.2059T>C NP_001395384.1:p.Trp687Arg missense NM_001408456.1:c.2059T>C NP_001395385.1:p.Trp687Arg missense NM_001408457.1:c.2059T>C NP_001395386.1:p.Trp687Arg missense NM_001408458.1:c.2056T>C NP_001395387.1:p.Trp686Arg missense NM_001408459.1:c.2056T>C NP_001395388.1:p.Trp686Arg missense NM_001408460.1:c.2056T>C NP_001395389.1:p.Trp686Arg missense NM_001408461.1:c.2056T>C NP_001395390.1:p.Trp686Arg missense NM_001408462.1:c.2056T>C NP_001395391.1:p.Trp686Arg missense NM_001408463.1:c.2056T>C NP_001395392.1:p.Trp686Arg missense NM_001408464.1:c.2056T>C NP_001395393.1:p.Trp686Arg missense NM_001408465.1:c.2056T>C NP_001395394.1:p.Trp686Arg missense NM_001408466.1:c.2056T>C NP_001395395.1:p.Trp686Arg missense NM_001408467.1:c.2056T>C NP_001395396.1:p.Trp686Arg missense NM_001408468.1:c.2053T>C NP_001395397.1:p.Trp685Arg missense NM_001408469.1:c.2053T>C NP_001395398.1:p.Trp685Arg missense NM_001408470.1:c.2053T>C NP_001395399.1:p.Trp685Arg missense NM_001408472.1:c.*23T>C NM_001408473.1:c.*23T>C NM_001408474.1:c.1999T>C NP_001395403.1:p.Trp667Arg missense NM_001408475.1:c.1996T>C NP_001395404.1:p.Trp666Arg missense NM_001408476.1:c.1996T>C NP_001395405.1:p.Trp666Arg missense NM_001408478.1:c.1990T>C NP_001395407.1:p.Trp664Arg missense NM_001408479.1:c.1990T>C NP_001395408.1:p.Trp664Arg missense NM_001408480.1:c.1990T>C NP_001395409.1:p.Trp664Arg missense NM_001408481.1:c.1987T>C NP_001395410.1:p.Trp663Arg missense NM_001408482.1:c.1987T>C NP_001395411.1:p.Trp663Arg missense NM_001408483.1:c.1987T>C NP_001395412.1:p.Trp663Arg missense NM_001408484.1:c.1987T>C NP_001395413.1:p.Trp663Arg missense NM_001408485.1:c.1987T>C NP_001395414.1:p.Trp663Arg missense NM_001408489.1:c.1987T>C NP_001395418.1:p.Trp663Arg missense NM_001408490.1:c.1987T>C NP_001395419.1:p.Trp663Arg missense NM_001408491.1:c.1987T>C NP_001395420.1:p.Trp663Arg missense NM_001408492.1:c.1984T>C NP_001395421.1:p.Trp662Arg missense NM_001408493.1:c.1984T>C NP_001395422.1:p.Trp662Arg missense NM_001408494.1:c.1960T>C NP_001395423.1:p.Trp654Arg missense NM_001408495.1:c.1954T>C NP_001395424.1:p.Trp652Arg missense NM_001408496.1:c.1936T>C NP_001395425.1:p.Trp646Arg missense NM_001408497.1:c.1936T>C NP_001395426.1:p.Trp646Arg missense NM_001408498.1:c.1936T>C NP_001395427.1:p.Trp646Arg missense NM_001408499.1:c.1936T>C NP_001395428.1:p.Trp646Arg missense NM_001408500.1:c.1936T>C NP_001395429.1:p.Trp646Arg missense NM_001408501.1:c.1936T>C NP_001395430.1:p.Trp646Arg missense NM_001408502.1:c.1933T>C NP_001395431.1:p.Trp645Arg missense NM_001408503.1:c.1933T>C NP_001395432.1:p.Trp645Arg missense NM_001408504.1:c.1933T>C NP_001395433.1:p.Trp645Arg missense NM_001408505.1:c.1930T>C NP_001395434.1:p.Trp644Arg missense NM_001408506.1:c.1873T>C NP_001395435.1:p.Trp625Arg missense NM_001408507.1:c.1870T>C NP_001395436.1:p.Trp624Arg missense NM_001408508.1:c.1861T>C NP_001395437.1:p.Trp621Arg missense NM_001408509.1:c.1858T>C NP_001395438.1:p.Trp620Arg missense NM_001408510.1:c.1819T>C NP_001395439.1:p.Trp607Arg missense NM_001408511.1:c.1816T>C NP_001395440.1:p.Trp606Arg missense NM_001408512.1:c.1696T>C NP_001395441.1:p.Trp566Arg missense NM_001408513.1:c.1669T>C NP_001395442.1:p.Trp557Arg missense NM_001408514.1:c.1273T>C NP_001395443.1:p.Trp425Arg missense NM_007297.4:c.5368T>C NP_009228.2:p.Trp1790Arg missense NM_007298.4:c.2197T>C NP_009229.2:p.Trp733Arg missense NM_007299.4:c.*23T>C 3 prime UTR NM_007300.4:c.5572T>C NP_009231.2:p.Trp1858Arg missense NM_007304.2:c.2197T>C NP_009235.2:p.Trp733Arg missense NR_027676.2:n.5686T>C non-coding transcript variant NC_000017.11:g.43045761A>G NC_000017.10:g.41197778A>G NG_005905.2:g.172223T>C LRG_292:g.172223T>C LRG_292t1:c.5509T>C LRG_292p1:p.Trp1837Arg P38398:p.Trp1837Arg U14680.1:n.5628T>C - Protein change
- W1837R, W733R, W1858R, W1790R, W1540R, W1541R, W1725R, W1747R, W1766R, W1768R, W1794R, W1817R, W425R, W621R, W624R, W625R, W646R, W662R, W663R, W685R, W691R, W707R, W731R, W1668R, W1683R, W1724R, W1765R, W1770R, W1789R, W1795R, W1796R, W1809R, W1810R, W1832R, W1857R, W1859R, W557R, W606R, W666R, W667R, W687R, W692R, W730R, W734R, W1708R, W1709R, W1710R, W1726R, W1767R, W1788R, W1818R, W1833R, W566R, W607R, W644R, W652R, W664R, W686R, W693R, W694R, W695R, W708R, W732R, W1748R, W1749R, W1753R, W1769R, W1793R, W1811R, W1834R, W1835R, W1836R, W620R, W645R, W654R, W689R, W709R, W755R, W756R, W968R, W969R
- Other names
- 5628T>C
- Canonical SPDI
- NC_000017.11:43045760:A:G
-
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.5509T>C, a MISSENSE variant, produced a function score of -2.31, 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.
-
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 |
13019 | 14822 |
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 (10) |
reviewed by expert panel
|
Jun 18, 2019 | RCV000031260.23 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 17, 2023 | RCV000129546.21 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 8, 2023 | RCV000236322.23 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000779893.15 |
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
(Jun 18, 2019)
|
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: SCV001161646.2
First in ClinVar: Feb 16, 2020 Last updated: Jan 07, 2023 |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on … (more)
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 0.991787 (less)
|
|
Pathogenic
(Aug 04, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469400.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. … (more)
Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein Two other pathogenic or likely pathogenic variants affect the same amino acid. Assessment of experimental evidence suggests this variant results in abnormal protein function. Inconclusive segregation with disease. (less)
|
|
Likely pathogenic
(Nov 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000184326.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.W1837R variant (also known as c.5509T>C), located in coding exon 22 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.W1837R variant (also known as c.5509T>C), located in coding exon 22 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5509. The tryptophan at codon 1837 is replaced by arginine, an amino acid with dissimilar properties. This variant has been seen in multiple ethnically diverse hereditary breast and ovarian cancer (HBOC) syndrome families (Montagna M et al. Cancer Res. 1996;56:5466-9; Fernandes GC et al. Oncotarget. 2016 Dec;7:80465-80481; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295(5):1227-1238; Zuntini R et al. Front Genet. 2018 Sep;9:378). In one study, p.W1837R was predicted to be a high-risk variant based on decreased transcription levels, segregation, protease sensitivity, and structural analyses. However, pedigree association analysis suggested that this alteration was not causative, and therefore the authors classified this as a VUS due to the conflicting information (Phelan CM et al. J. Med. Genet. 2005;42:138-46). The p.W1837R variant was also predicted to be likely pathogenic based on functional studies showing 3% structural stability, less than 10% protease sensitivity, roughly 20% binding activity, less than 20% binding specificity, and less than 20% transcription activity (Lee MS et al. Cancer Res. 2010;70:4880-90). One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature. 2018 10;562(7726):217-222). This alteration has been predicted to be deleterious in several other functional and computational studies as well (Williams RS et al. J. Biol. Chem. 2003; 278:53007-16; Abkevich V et al. J. Med. Genet. 2004;41:492-507; Karchin R et al. PLoS Comput. Biol. 2007;3:e26; Bouwman P et al. Cancer Discov. 2013 Oct;3(10):1142-55; Gaiser OJ et al. Biochemistry. 2004 Dec;43:15983-95; Mirkovic N et al. Cancer Res. 2004 Jun;64:3790-7; Woods NT et al. NPJ Genom Med. 2016 Mar). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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Likely pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140463.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(Feb 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004215199.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916785.3
First in ClinVar: Jun 02, 2019 Last updated: Apr 15, 2024 |
Comment:
Variant summary: BRCA1 c.5509T>C (p.Trp1837Arg) results in a non-conservative amino acid change located in the BRCT domain of the encoded protein sequence. Five of five … (more)
Variant summary: BRCA1 c.5509T>C (p.Trp1837Arg) results in a non-conservative amino acid change located in the BRCT domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Multiple functional studies from different model systems showed mutant protein with decreased stability and solubility, compromised substrate binding activity, increased protease sensitivity, decreased transcription activation level, non-functional HDR pathway and increased cisplatin sensitivity (Phelan_2005, Bouwman_2013, Williams_2003, Lee_ 2010, and Rowling _2010, Findlay_2018), suggesting a defective function of the protein associated with this variant. Structural 3-D modeling study and comparative sequence alignment studies predicted the variant to be cancer-associated or likely to be deleterious (Mirkovic_2004 and Abkevich _2004, respectively). The variant was absent in 247618 control chromosomes (gnomAD). This variant has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Montagna _1996, Meisel_2017, Fernandes_2016, Zanella_2017, Azzollini_2016, Park_2017, Phelan_2005, Zuntini_2018). In one report, the variant was shown to segregate with disease in two affected family members (Zutini_2018). However, in one family the variant was identified in a father with prostate cancer and in his daughter who had breast cancer at age 39 but it was absent in two cousins of the proband affected with breast and bladder cancer (Phelan_2005), which may suggest lack of co-segregation of the variant with the disease or another pathogenic variant may present in this family. The following publications have been ascertained in the context of this evaluation (PMID: 15235020, 27062684, 23867111, 17005433, 27741520, 30209399, 21447777, 17305420, 20516115, 11802209, 28324225, 15172985, 8968102, 28111427, 15689452, 20378548, 14534301, 28781887, 28263838, 30254663). ClinVar contains an entry for this variant (Variation ID: 37679). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Dec 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004704337.6
First in ClinVar: Mar 10, 2024 Last updated: Aug 04, 2024 |
Comment:
BRCA1: PS1, PM2, PM5, PS3:Moderate, PS4:Moderate, BP1
Number of individuals with the variant: 1
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Pathogenic
(Dec 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000292710.13
First in ClinVar: Jul 24, 2016 Last updated: Sep 16, 2024 |
Comment:
Observed in several individuals with a personal or family history of BRCA1-related cancers (PMID: 8968102, 11802209, 15689452, 27741520, 30103829, 29791287, 30254663); Published functional studies demonstrate … (more)
Observed in several individuals with a personal or family history of BRCA1-related cancers (PMID: 8968102, 11802209, 15689452, 27741520, 30103829, 29791287, 30254663); Published functional studies demonstrate a damaging effect: decreased transactivation activity, destabilized BRCA1 protein, and decreased cell survival (PMID: 14534301, 15689452, 20516115, 20378548, 30209399, 35665744); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5628T>C; This variant is associated with the following publications: (PMID: 14534301, 30103829, 17305420, 21447777, 16969499, 15235020, 8968102, 23867111, 15689452, 20516115, 15172985, 28781887, 30209399, 30415210, 28111427, 20378548, 18036263, 17005433, 16786532, 16528612, 15609993, 11802209, 29791287, 27741520, 30254663, 28263838, 28324225, 29907814, 29470806, 30765603, 30736435, 34597585, 32719484, 34645131, 32546644, 31907386, 31131967, 33087888, 35459234, 35665744, 25348405) (less)
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Likely pathogenic
(Nov 07, 2017)
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criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000785711.2
First in ClinVar: May 27, 2015 Last updated: May 27, 2015 |
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Likely pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499667.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
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Likely 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: SCV002003983.1
First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021 |
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Pathogenic
(Jan 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001578228.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1837 of the BRCA1 protein … (more)
This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1837 of the BRCA1 protein (p.Trp1837Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8968102, 11802209, 15689452, 27741520, 28324225; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 37679). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 14534301, 15689452, 17305420, 20516115, 23867111, 30209399). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 08, 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
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000908978.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces tryptophan with arginine at codon 1837 of the BRCA1 protein. Computational models consistently predict deleterious impact of this variant on protein … (more)
This missense variant replaces tryptophan with arginine at codon 1837 of the BRCA1 protein. Computational models consistently predict deleterious impact of this variant on protein structure and function (PMID: 15172985, 15235020, 15609993, 17305420, 27666373). Functional studies have shown that this variant alters protease sensitivity, structural stability, substrate binding, transcriptional activation, a DNA repair pathway, and sensitivity to chemotherapies (PMID: 14534301, 15689452, 16969499, 17305420, 20378548, 20516115, 21447777, 23867111, 28781887, 30209399, 30765603, 32546644). This variant has been reported in individuals affected with early-onset breast cancer, ovarian cancer, and prostate cancer (PMID: 8968102, 11802209, 15689452, 27741520, 28111427, 28263838, 28324225, 29907814, 29907814, 30103829, 30254663). In three families, the variant was identified in an affected parent and their affected child (PMID: 8968102, 15689452, 30254663). Several probability-based multifactorial likelihood models classify the variant as Pathogenic (PMID: 30415210, 31131967, 32546644). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Likely pathogenic
(Nov 17, 2010)
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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
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053864.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Uncertain significance
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145556.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 3
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 3:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741447.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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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: SCV001956059.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Sep 01, 2023)
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no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical and Surgical Sciences, University of Bologna
Accession: SCV004228371.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
PS3(Strong)+PM2(Supporting)+PP4(Very Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
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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: SCV001243483.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.31441872512525
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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
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. |
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001243483.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5509T>C, a MISSENSE variant, produced a function score of -2.31, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5509T>C, a MISSENSE variant, produced a function score of -2.31, 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)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Functional Categorization of BRCA1 Variants of Uncertain Clinical Significance in Homologous Recombination Repair Complementation Assays. | Bouwman P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2020 | PMID: 32546644 |
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort. | Lee JS | Journal of medical genetics | 2018 | PMID: 30415210 |
Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help? | Zuntini R | Frontiers in genetics | 2018 | PMID: 30254663 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population. | Cardoso FC | Human genomics | 2018 | PMID: 30103829 |
The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. | Singh J | Breast cancer research and treatment | 2018 | PMID: 29470806 |
Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
Evaluation of the Ion Torrent PGM sequencing workflow for the routine rapid detection of BRCA1 and BRCA2 germline mutations. | Zanella I | Experimental and molecular pathology | 2017 | PMID: 28263838 |
Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. | Park JS | Cancer research and treatment | 2017 | PMID: 28111427 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
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 |
REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. | Ioannidis NM | American journal of human genetics | 2016 | PMID: 27666373 |
Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families: A monocentric Italian study. | Azzollini J | European journal of internal medicine | 2016 | PMID: 27062684 |
A high-throughput functional complementation assay for classification of BRCA1 missense variants. | Bouwman P | Cancer discovery | 2013 | PMID: 23867111 |
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 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Toward classification of BRCA1 missense variants using a biophysical approach. | Rowling PJ | The Journal of biological chemistry | 2010 | PMID: 20378548 |
Functional impact of missense variants in BRCA1 predicted by supervised learning. | Karchin R | PLoS computational biology | 2007 | PMID: 17305420 |
Specific changes in the proteomic pattern produced by the BRCA1-Ser1841Asn missense mutation. | Crugliano T | The international journal of biochemistry & cell biology | 2007 | PMID: 17005433 |
Missense mutations of BRCA1 gene affect the binding with p53 both in vitro and in vivo. | Quaresima B | Oncology reports | 2006 | PMID: 16969499 |
Classification of BRCA1 missense variants of unknown clinical significance. | Phelan CM | Journal of medical genetics | 2005 | PMID: 15689452 |
Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1. | Gaiser OJ | Biochemistry | 2004 | PMID: 15609993 |
Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. | Mirkovic N | Cancer research | 2004 | PMID: 15172985 |
Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. | Williams RS | The Journal of biological chemistry | 2003 | PMID: 14534301 |
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. | Meindl A | International journal of cancer | 2002 | PMID: 11802209 |
Identification of seven new BRCA1 germline mutations in Italian breast and breast/ovarian cancer families. | Montagna M | Cancer research | 1996 | PMID: 8968102 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80356959 ...
HelpRecord last updated Sep 17, 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.