ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5511G>C (p.Trp1837Cys)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5511G>C (p.Trp1837Cys)
Variation ID: 421244 Accession: VCV000421244.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045759 (GRCh38) [ NCBI UCSC ] 17: 41197776 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 29, 2017 Feb 20, 2024 May 15, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_007294.4:c.5511G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Trp1837Cys missense NM_001407571.1:c.5298G>C NP_001394500.1:p.Trp1766Cys missense NM_001407581.1:c.5577G>C NP_001394510.1:p.Trp1859Cys missense NM_001407582.1:c.5577G>C NP_001394511.1:p.Trp1859Cys missense NM_001407583.1:c.5574G>C NP_001394512.1:p.Trp1858Cys missense NM_001407585.1:c.5574G>C NP_001394514.1:p.Trp1858Cys missense NM_001407587.1:c.5574G>C NP_001394516.1:p.Trp1858Cys missense NM_001407590.1:c.5571G>C NP_001394519.1:p.Trp1857Cys missense NM_001407591.1:c.5571G>C NP_001394520.1:p.Trp1857Cys missense NM_001407593.1:c.5511G>C NP_001394522.1:p.Trp1837Cys missense NM_001407594.1:c.5511G>C NP_001394523.1:p.Trp1837Cys missense NM_001407596.1:c.5511G>C NP_001394525.1:p.Trp1837Cys missense NM_001407597.1:c.5511G>C NP_001394526.1:p.Trp1837Cys missense NM_001407598.1:c.5511G>C NP_001394527.1:p.Trp1837Cys missense NM_001407602.1:c.5511G>C NP_001394531.1:p.Trp1837Cys missense NM_001407603.1:c.5511G>C NP_001394532.1:p.Trp1837Cys missense NM_001407605.1:c.5511G>C NP_001394534.1:p.Trp1837Cys missense NM_001407610.1:c.5508G>C NP_001394539.1:p.Trp1836Cys missense NM_001407611.1:c.5508G>C NP_001394540.1:p.Trp1836Cys missense NM_001407612.1:c.5508G>C NP_001394541.1:p.Trp1836Cys missense NM_001407613.1:c.5508G>C NP_001394542.1:p.Trp1836Cys missense NM_001407614.1:c.5508G>C NP_001394543.1:p.Trp1836Cys missense NM_001407615.1:c.5508G>C NP_001394544.1:p.Trp1836Cys missense NM_001407616.1:c.5508G>C NP_001394545.1:p.Trp1836Cys missense NM_001407617.1:c.5508G>C NP_001394546.1:p.Trp1836Cys missense NM_001407618.1:c.5508G>C NP_001394547.1:p.Trp1836Cys missense NM_001407619.1:c.5508G>C NP_001394548.1:p.Trp1836Cys missense NM_001407620.1:c.5508G>C NP_001394549.1:p.Trp1836Cys missense NM_001407621.1:c.5508G>C NP_001394550.1:p.Trp1836Cys missense NM_001407622.1:c.5508G>C NP_001394551.1:p.Trp1836Cys missense NM_001407623.1:c.5508G>C NP_001394552.1:p.Trp1836Cys missense NM_001407624.1:c.5508G>C NP_001394553.1:p.Trp1836Cys missense NM_001407625.1:c.5508G>C NP_001394554.1:p.Trp1836Cys missense NM_001407626.1:c.5508G>C NP_001394555.1:p.Trp1836Cys missense NM_001407627.1:c.5505G>C NP_001394556.1:p.Trp1835Cys missense NM_001407628.1:c.5505G>C NP_001394557.1:p.Trp1835Cys missense NM_001407629.1:c.5505G>C NP_001394558.1:p.Trp1835Cys missense NM_001407630.1:c.5505G>C NP_001394559.1:p.Trp1835Cys missense NM_001407631.1:c.5505G>C NP_001394560.1:p.Trp1835Cys missense NM_001407632.1:c.5505G>C NP_001394561.1:p.Trp1835Cys missense NM_001407633.1:c.5505G>C NP_001394562.1:p.Trp1835Cys missense NM_001407634.1:c.5505G>C NP_001394563.1:p.Trp1835Cys missense NM_001407635.1:c.5505G>C NP_001394564.1:p.Trp1835Cys missense NM_001407636.1:c.5505G>C NP_001394565.1:p.Trp1835Cys missense NM_001407637.1:c.5505G>C NP_001394566.1:p.Trp1835Cys missense NM_001407638.1:c.5505G>C NP_001394567.1:p.Trp1835Cys missense NM_001407639.1:c.5505G>C NP_001394568.1:p.Trp1835Cys missense NM_001407640.1:c.5505G>C NP_001394569.1:p.Trp1835Cys missense NM_001407641.1:c.5505G>C NP_001394570.1:p.Trp1835Cys missense NM_001407642.1:c.5505G>C NP_001394571.1:p.Trp1835Cys missense NM_001407644.1:c.5502G>C NP_001394573.1:p.Trp1834Cys missense NM_001407645.1:c.5502G>C NP_001394574.1:p.Trp1834Cys missense NM_001407646.1:c.5499G>C NP_001394575.1:p.Trp1833Cys missense NM_001407647.1:c.5496G>C NP_001394576.1:p.Trp1832Cys missense NM_001407648.1:c.5454G>C NP_001394577.1:p.Trp1818Cys missense NM_001407649.1:c.5451G>C NP_001394578.1:p.Trp1817Cys missense NM_001407652.1:c.5433G>C NP_001394581.1:p.Trp1811Cys missense NM_001407653.1:c.5433G>C NP_001394582.1:p.Trp1811Cys missense NM_001407654.1:c.5433G>C NP_001394583.1:p.Trp1811Cys missense NM_001407655.1:c.5433G>C NP_001394584.1:p.Trp1811Cys missense NM_001407656.1:c.5430G>C NP_001394585.1:p.Trp1810Cys missense NM_001407657.1:c.5430G>C NP_001394586.1:p.Trp1810Cys missense NM_001407658.1:c.5430G>C NP_001394587.1:p.Trp1810Cys missense NM_001407659.1:c.5427G>C NP_001394588.1:p.Trp1809Cys missense NM_001407660.1:c.5427G>C NP_001394589.1:p.Trp1809Cys missense NM_001407661.1:c.5427G>C NP_001394590.1:p.Trp1809Cys missense NM_001407662.1:c.5427G>C NP_001394591.1:p.Trp1809Cys missense NM_001407663.1:c.5427G>C NP_001394592.1:p.Trp1809Cys missense NM_001407664.1:c.5388G>C NP_001394593.1:p.Trp1796Cys missense NM_001407665.1:c.5388G>C NP_001394594.1:p.Trp1796Cys missense NM_001407666.1:c.5388G>C NP_001394595.1:p.Trp1796Cys missense NM_001407667.1:c.5388G>C NP_001394596.1:p.Trp1796Cys missense NM_001407668.1:c.5388G>C NP_001394597.1:p.Trp1796Cys missense NM_001407669.1:c.5388G>C NP_001394598.1:p.Trp1796Cys missense NM_001407670.1:c.5385G>C NP_001394599.1:p.Trp1795Cys missense NM_001407671.1:c.5385G>C NP_001394600.1:p.Trp1795Cys missense NM_001407672.1:c.5385G>C NP_001394601.1:p.Trp1795Cys missense NM_001407673.1:c.5385G>C NP_001394602.1:p.Trp1795Cys missense NM_001407674.1:c.5385G>C NP_001394603.1:p.Trp1795Cys missense NM_001407675.1:c.5385G>C NP_001394604.1:p.Trp1795Cys missense NM_001407676.1:c.5385G>C NP_001394605.1:p.Trp1795Cys missense NM_001407677.1:c.5385G>C NP_001394606.1:p.Trp1795Cys missense NM_001407678.1:c.5385G>C NP_001394607.1:p.Trp1795Cys missense NM_001407679.1:c.5385G>C NP_001394608.1:p.Trp1795Cys missense NM_001407680.1:c.5385G>C NP_001394609.1:p.Trp1795Cys missense NM_001407681.1:c.5382G>C NP_001394610.1:p.Trp1794Cys missense NM_001407682.1:c.5382G>C NP_001394611.1:p.Trp1794Cys missense NM_001407683.1:c.5382G>C NP_001394612.1:p.Trp1794Cys missense NM_001407684.1:c.5382G>C NP_001394613.1:p.Trp1794Cys missense NM_001407685.1:c.5382G>C NP_001394614.1:p.Trp1794Cys missense NM_001407686.1:c.5382G>C NP_001394615.1:p.Trp1794Cys missense NM_001407687.1:c.5382G>C NP_001394616.1:p.Trp1794Cys missense NM_001407688.1:c.5382G>C NP_001394617.1:p.Trp1794Cys missense NM_001407689.1:c.5382G>C NP_001394618.1:p.Trp1794Cys missense NM_001407690.1:c.5379G>C NP_001394619.1:p.Trp1793Cys missense NM_001407691.1:c.5379G>C NP_001394620.1:p.Trp1793Cys missense NM_001407692.1:c.5370G>C NP_001394621.1:p.Trp1790Cys missense NM_001407694.1:c.5370G>C NP_001394623.1:p.Trp1790Cys missense NM_001407695.1:c.5370G>C NP_001394624.1:p.Trp1790Cys missense NM_001407696.1:c.5370G>C NP_001394625.1:p.Trp1790Cys missense NM_001407697.1:c.5370G>C NP_001394626.1:p.Trp1790Cys missense NM_001407698.1:c.5370G>C NP_001394627.1:p.Trp1790Cys missense NM_001407724.1:c.5370G>C NP_001394653.1:p.Trp1790Cys missense NM_001407725.1:c.5370G>C NP_001394654.1:p.Trp1790Cys missense NM_001407726.1:c.5370G>C NP_001394655.1:p.Trp1790Cys missense NM_001407727.1:c.5370G>C NP_001394656.1:p.Trp1790Cys missense NM_001407728.1:c.5370G>C NP_001394657.1:p.Trp1790Cys missense NM_001407729.1:c.5370G>C NP_001394658.1:p.Trp1790Cys missense NM_001407730.1:c.5370G>C NP_001394659.1:p.Trp1790Cys missense NM_001407731.1:c.5370G>C NP_001394660.1:p.Trp1790Cys missense NM_001407732.1:c.5367G>C NP_001394661.1:p.Trp1789Cys missense NM_001407733.1:c.5367G>C NP_001394662.1:p.Trp1789Cys missense NM_001407734.1:c.5367G>C NP_001394663.1:p.Trp1789Cys missense NM_001407735.1:c.5367G>C NP_001394664.1:p.Trp1789Cys missense NM_001407736.1:c.5367G>C NP_001394665.1:p.Trp1789Cys missense NM_001407737.1:c.5367G>C NP_001394666.1:p.Trp1789Cys missense NM_001407738.1:c.5367G>C NP_001394667.1:p.Trp1789Cys missense NM_001407739.1:c.5367G>C NP_001394668.1:p.Trp1789Cys missense NM_001407740.1:c.5367G>C NP_001394669.1:p.Trp1789Cys missense NM_001407741.1:c.5367G>C NP_001394670.1:p.Trp1789Cys missense NM_001407742.1:c.5367G>C NP_001394671.1:p.Trp1789Cys missense NM_001407743.1:c.5367G>C NP_001394672.1:p.Trp1789Cys missense NM_001407744.1:c.5367G>C NP_001394673.1:p.Trp1789Cys missense NM_001407745.1:c.5367G>C NP_001394674.1:p.Trp1789Cys missense NM_001407746.1:c.5367G>C NP_001394675.1:p.Trp1789Cys missense NM_001407747.1:c.5367G>C NP_001394676.1:p.Trp1789Cys missense NM_001407748.1:c.5367G>C NP_001394677.1:p.Trp1789Cys missense NM_001407749.1:c.5367G>C NP_001394678.1:p.Trp1789Cys missense NM_001407750.1:c.5367G>C NP_001394679.1:p.Trp1789Cys missense NM_001407751.1:c.5367G>C NP_001394680.1:p.Trp1789Cys missense NM_001407752.1:c.5367G>C NP_001394681.1:p.Trp1789Cys missense NM_001407838.1:c.5364G>C NP_001394767.1:p.Trp1788Cys missense NM_001407839.1:c.5364G>C NP_001394768.1:p.Trp1788Cys missense NM_001407841.1:c.5364G>C NP_001394770.1:p.Trp1788Cys missense NM_001407842.1:c.5364G>C NP_001394771.1:p.Trp1788Cys missense NM_001407843.1:c.5364G>C NP_001394772.1:p.Trp1788Cys missense NM_001407844.1:c.5364G>C NP_001394773.1:p.Trp1788Cys missense NM_001407845.1:c.5364G>C NP_001394774.1:p.Trp1788Cys missense NM_001407846.1:c.5364G>C NP_001394775.1:p.Trp1788Cys missense NM_001407847.1:c.5364G>C NP_001394776.1:p.Trp1788Cys missense NM_001407848.1:c.5364G>C NP_001394777.1:p.Trp1788Cys missense NM_001407849.1:c.5364G>C NP_001394778.1:p.Trp1788Cys missense NM_001407850.1:c.5364G>C NP_001394779.1:p.Trp1788Cys missense NM_001407851.1:c.5364G>C NP_001394780.1:p.Trp1788Cys missense NM_001407852.1:c.5364G>C NP_001394781.1:p.Trp1788Cys missense NM_001407853.1:c.5364G>C NP_001394782.1:p.Trp1788Cys missense NM_001407854.1:c.*25G>C NM_001407858.1:c.*25G>C NM_001407859.1:c.*25G>C NM_001407860.1:c.*25G>C NM_001407861.1:c.*25G>C NM_001407862.1:c.5310G>C NP_001394791.1:p.Trp1770Cys missense NM_001407863.1:c.5307G>C NP_001394792.1:p.Trp1769Cys missense NM_001407874.1:c.5304G>C NP_001394803.1:p.Trp1768Cys missense NM_001407875.1:c.5304G>C NP_001394804.1:p.Trp1768Cys missense NM_001407879.1:c.5301G>C NP_001394808.1:p.Trp1767Cys missense NM_001407881.1:c.5301G>C NP_001394810.1:p.Trp1767Cys missense NM_001407882.1:c.5301G>C NP_001394811.1:p.Trp1767Cys missense NM_001407884.1:c.5301G>C NP_001394813.1:p.Trp1767Cys missense NM_001407885.1:c.5301G>C NP_001394814.1:p.Trp1767Cys missense NM_001407886.1:c.5301G>C NP_001394815.1:p.Trp1767Cys missense NM_001407887.1:c.5301G>C NP_001394816.1:p.Trp1767Cys missense NM_001407889.1:c.5301G>C NP_001394818.1:p.Trp1767Cys missense NM_001407894.1:c.5298G>C NP_001394823.1:p.Trp1766Cys missense NM_001407895.1:c.5298G>C NP_001394824.1:p.Trp1766Cys missense NM_001407896.1:c.5298G>C NP_001394825.1:p.Trp1766Cys missense NM_001407897.1:c.5298G>C NP_001394826.1:p.Trp1766Cys missense NM_001407898.1:c.5298G>C NP_001394827.1:p.Trp1766Cys missense NM_001407899.1:c.5298G>C NP_001394828.1:p.Trp1766Cys missense NM_001407900.1:c.5298G>C NP_001394829.1:p.Trp1766Cys missense NM_001407902.1:c.5298G>C NP_001394831.1:p.Trp1766Cys missense NM_001407904.1:c.5298G>C NP_001394833.1:p.Trp1766Cys missense NM_001407906.1:c.5298G>C NP_001394835.1:p.Trp1766Cys missense NM_001407907.1:c.5298G>C NP_001394836.1:p.Trp1766Cys missense NM_001407908.1:c.5298G>C NP_001394837.1:p.Trp1766Cys missense NM_001407909.1:c.5298G>C NP_001394838.1:p.Trp1766Cys missense NM_001407910.1:c.5298G>C NP_001394839.1:p.Trp1766Cys missense NM_001407915.1:c.5295G>C NP_001394844.1:p.Trp1765Cys missense NM_001407916.1:c.5295G>C NP_001394845.1:p.Trp1765Cys missense NM_001407917.1:c.5295G>C NP_001394846.1:p.Trp1765Cys missense NM_001407918.1:c.5295G>C NP_001394847.1:p.Trp1765Cys missense NM_001407919.1:c.5259G>C NP_001394848.1:p.Trp1753Cys missense NM_001407920.1:c.5247G>C NP_001394849.1:p.Trp1749Cys missense NM_001407921.1:c.5247G>C NP_001394850.1:p.Trp1749Cys missense NM_001407922.1:c.5247G>C NP_001394851.1:p.Trp1749Cys missense NM_001407923.1:c.5247G>C NP_001394852.1:p.Trp1749Cys missense NM_001407924.1:c.5247G>C NP_001394853.1:p.Trp1749Cys missense NM_001407925.1:c.5247G>C NP_001394854.1:p.Trp1749Cys missense NM_001407926.1:c.5247G>C NP_001394855.1:p.Trp1749Cys missense NM_001407927.1:c.5244G>C NP_001394856.1:p.Trp1748Cys missense NM_001407928.1:c.5244G>C NP_001394857.1:p.Trp1748Cys missense NM_001407929.1:c.5244G>C NP_001394858.1:p.Trp1748Cys missense NM_001407930.1:c.5244G>C NP_001394859.1:p.Trp1748Cys missense NM_001407931.1:c.5244G>C NP_001394860.1:p.Trp1748Cys missense NM_001407932.1:c.5244G>C NP_001394861.1:p.Trp1748Cys missense NM_001407933.1:c.5244G>C NP_001394862.1:p.Trp1748Cys missense NM_001407934.1:c.5241G>C NP_001394863.1:p.Trp1747Cys missense NM_001407935.1:c.5241G>C NP_001394864.1:p.Trp1747Cys missense NM_001407936.1:c.5241G>C NP_001394865.1:p.Trp1747Cys missense NM_001407937.1:c.*25G>C NM_001407938.1:c.*25G>C NM_001407939.1:c.*25G>C NM_001407940.1:c.*25G>C NM_001407941.1:c.*25G>C NM_001407942.1:c.*25G>C NM_001407943.1:c.*25G>C NM_001407944.1:c.*25G>C NM_001407945.1:c.*25G>C NM_001407946.1:c.5178G>C NP_001394875.1:p.Trp1726Cys missense NM_001407947.1:c.5178G>C NP_001394876.1:p.Trp1726Cys missense NM_001407948.1:c.5178G>C NP_001394877.1:p.Trp1726Cys missense NM_001407949.1:c.5178G>C NP_001394878.1:p.Trp1726Cys missense NM_001407950.1:c.5175G>C NP_001394879.1:p.Trp1725Cys missense NM_001407951.1:c.5175G>C NP_001394880.1:p.Trp1725Cys missense NM_001407952.1:c.5175G>C NP_001394881.1:p.Trp1725Cys missense NM_001407953.1:c.5175G>C NP_001394882.1:p.Trp1725Cys missense NM_001407954.1:c.5175G>C NP_001394883.1:p.Trp1725Cys missense NM_001407955.1:c.5175G>C NP_001394884.1:p.Trp1725Cys missense NM_001407956.1:c.5172G>C NP_001394885.1:p.Trp1724Cys missense NM_001407957.1:c.5172G>C NP_001394886.1:p.Trp1724Cys missense NM_001407958.1:c.5172G>C NP_001394887.1:p.Trp1724Cys missense NM_001407959.1:c.5130G>C NP_001394888.1:p.Trp1710Cys missense NM_001407960.1:c.5127G>C NP_001394889.1:p.Trp1709Cys missense NM_001407962.1:c.5127G>C NP_001394891.1:p.Trp1709Cys missense NM_001407963.1:c.5124G>C NP_001394892.1:p.Trp1708Cys missense NM_001407964.1:c.5049G>C NP_001394893.1:p.Trp1683Cys missense NM_001407965.1:c.5004G>C NP_001394894.1:p.Trp1668Cys missense NM_001407966.1:c.4623G>C NP_001394895.1:p.Trp1541Cys missense NM_001407967.1:c.4620G>C NP_001394896.1:p.Trp1540Cys missense NM_001407968.1:c.2907G>C NP_001394897.1:p.Trp969Cys missense NM_001407969.1:c.2904G>C NP_001394898.1:p.Trp968Cys missense NM_001407970.1:c.2268G>C NP_001394899.1:p.Trp756Cys missense NM_001407971.1:c.2268G>C NP_001394900.1:p.Trp756Cys missense NM_001407972.1:c.2265G>C NP_001394901.1:p.Trp755Cys missense NM_001407973.1:c.2202G>C NP_001394902.1:p.Trp734Cys missense NM_001407974.1:c.2202G>C NP_001394903.1:p.Trp734Cys missense NM_001407975.1:c.2202G>C NP_001394904.1:p.Trp734Cys missense NM_001407976.1:c.2202G>C NP_001394905.1:p.Trp734Cys missense NM_001407977.1:c.2202G>C NP_001394906.1:p.Trp734Cys missense NM_001407978.1:c.2202G>C NP_001394907.1:p.Trp734Cys missense NM_001407979.1:c.2199G>C NP_001394908.1:p.Trp733Cys missense NM_001407980.1:c.2199G>C NP_001394909.1:p.Trp733Cys missense NM_001407981.1:c.2199G>C NP_001394910.1:p.Trp733Cys missense NM_001407982.1:c.2199G>C NP_001394911.1:p.Trp733Cys missense NM_001407983.1:c.2199G>C NP_001394912.1:p.Trp733Cys missense NM_001407984.1:c.2199G>C NP_001394913.1:p.Trp733Cys missense NM_001407985.1:c.2199G>C NP_001394914.1:p.Trp733Cys missense NM_001407986.1:c.2199G>C NP_001394915.1:p.Trp733Cys missense NM_001407990.1:c.2199G>C NP_001394919.1:p.Trp733Cys missense NM_001407991.1:c.2199G>C NP_001394920.1:p.Trp733Cys missense NM_001407992.1:c.2199G>C NP_001394921.1:p.Trp733Cys missense NM_001407993.1:c.2199G>C NP_001394922.1:p.Trp733Cys missense NM_001408392.1:c.2196G>C NP_001395321.1:p.Trp732Cys missense NM_001408396.1:c.2196G>C NP_001395325.1:p.Trp732Cys missense NM_001408397.1:c.2196G>C NP_001395326.1:p.Trp732Cys missense NM_001408398.1:c.2196G>C NP_001395327.1:p.Trp732Cys missense NM_001408399.1:c.2196G>C NP_001395328.1:p.Trp732Cys missense NM_001408400.1:c.2196G>C NP_001395329.1:p.Trp732Cys missense NM_001408401.1:c.2196G>C NP_001395330.1:p.Trp732Cys missense NM_001408402.1:c.2196G>C NP_001395331.1:p.Trp732Cys missense NM_001408403.1:c.2196G>C NP_001395332.1:p.Trp732Cys missense NM_001408404.1:c.2196G>C NP_001395333.1:p.Trp732Cys missense NM_001408406.1:c.2193G>C NP_001395335.1:p.Trp731Cys missense NM_001408407.1:c.2193G>C NP_001395336.1:p.Trp731Cys missense NM_001408408.1:c.2193G>C NP_001395337.1:p.Trp731Cys missense NM_001408409.1:c.2190G>C NP_001395338.1:p.Trp730Cys missense NM_001408410.1:c.2127G>C NP_001395339.1:p.Trp709Cys missense NM_001408411.1:c.2124G>C NP_001395340.1:p.Trp708Cys missense NM_001408412.1:c.2121G>C NP_001395341.1:p.Trp707Cys missense NM_001408413.1:c.2121G>C NP_001395342.1:p.Trp707Cys missense NM_001408414.1:c.2121G>C NP_001395343.1:p.Trp707Cys missense NM_001408415.1:c.2121G>C NP_001395344.1:p.Trp707Cys missense NM_001408416.1:c.2121G>C NP_001395345.1:p.Trp707Cys missense NM_001408418.1:c.2085G>C NP_001395347.1:p.Trp695Cys missense NM_001408419.1:c.2085G>C NP_001395348.1:p.Trp695Cys missense NM_001408420.1:c.2085G>C NP_001395349.1:p.Trp695Cys missense NM_001408421.1:c.2082G>C NP_001395350.1:p.Trp694Cys missense NM_001408422.1:c.2082G>C NP_001395351.1:p.Trp694Cys missense NM_001408423.1:c.2082G>C NP_001395352.1:p.Trp694Cys missense NM_001408424.1:c.2082G>C NP_001395353.1:p.Trp694Cys missense NM_001408425.1:c.2079G>C NP_001395354.1:p.Trp693Cys missense NM_001408426.1:c.2079G>C NP_001395355.1:p.Trp693Cys missense NM_001408427.1:c.2079G>C NP_001395356.1:p.Trp693Cys missense NM_001408428.1:c.2079G>C NP_001395357.1:p.Trp693Cys missense NM_001408429.1:c.2079G>C NP_001395358.1:p.Trp693Cys missense NM_001408430.1:c.2079G>C NP_001395359.1:p.Trp693Cys missense NM_001408431.1:c.2079G>C NP_001395360.1:p.Trp693Cys missense NM_001408432.1:c.2076G>C NP_001395361.1:p.Trp692Cys missense NM_001408433.1:c.2076G>C NP_001395362.1:p.Trp692Cys missense NM_001408434.1:c.2076G>C NP_001395363.1:p.Trp692Cys missense NM_001408435.1:c.2076G>C NP_001395364.1:p.Trp692Cys missense NM_001408436.1:c.2076G>C NP_001395365.1:p.Trp692Cys missense NM_001408437.1:c.2076G>C NP_001395366.1:p.Trp692Cys missense NM_001408438.1:c.2076G>C NP_001395367.1:p.Trp692Cys missense NM_001408439.1:c.2076G>C NP_001395368.1:p.Trp692Cys missense NM_001408440.1:c.2076G>C NP_001395369.1:p.Trp692Cys missense NM_001408441.1:c.2076G>C NP_001395370.1:p.Trp692Cys missense NM_001408442.1:c.2076G>C NP_001395371.1:p.Trp692Cys missense NM_001408443.1:c.2076G>C NP_001395372.1:p.Trp692Cys missense NM_001408444.1:c.2076G>C NP_001395373.1:p.Trp692Cys missense NM_001408445.1:c.2073G>C NP_001395374.1:p.Trp691Cys missense NM_001408446.1:c.2073G>C NP_001395375.1:p.Trp691Cys missense NM_001408447.1:c.2073G>C NP_001395376.1:p.Trp691Cys missense NM_001408448.1:c.2073G>C NP_001395377.1:p.Trp691Cys missense NM_001408450.1:c.2073G>C NP_001395379.1:p.Trp691Cys missense NM_001408451.1:c.2067G>C NP_001395380.1:p.Trp689Cys missense NM_001408452.1:c.2061G>C NP_001395381.1:p.Trp687Cys missense NM_001408453.1:c.2061G>C NP_001395382.1:p.Trp687Cys missense NM_001408454.1:c.2061G>C NP_001395383.1:p.Trp687Cys missense NM_001408455.1:c.2061G>C NP_001395384.1:p.Trp687Cys missense NM_001408456.1:c.2061G>C NP_001395385.1:p.Trp687Cys missense NM_001408457.1:c.2061G>C NP_001395386.1:p.Trp687Cys missense NM_001408458.1:c.2058G>C NP_001395387.1:p.Trp686Cys missense NM_001408459.1:c.2058G>C NP_001395388.1:p.Trp686Cys missense NM_001408460.1:c.2058G>C NP_001395389.1:p.Trp686Cys missense NM_001408461.1:c.2058G>C NP_001395390.1:p.Trp686Cys missense NM_001408462.1:c.2058G>C NP_001395391.1:p.Trp686Cys missense NM_001408463.1:c.2058G>C NP_001395392.1:p.Trp686Cys missense NM_001408464.1:c.2058G>C NP_001395393.1:p.Trp686Cys missense NM_001408465.1:c.2058G>C NP_001395394.1:p.Trp686Cys missense NM_001408466.1:c.2058G>C NP_001395395.1:p.Trp686Cys missense NM_001408467.1:c.2058G>C NP_001395396.1:p.Trp686Cys missense NM_001408468.1:c.2055G>C NP_001395397.1:p.Trp685Cys missense NM_001408469.1:c.2055G>C NP_001395398.1:p.Trp685Cys missense NM_001408470.1:c.2055G>C NP_001395399.1:p.Trp685Cys missense NM_001408472.1:c.*25G>C NM_001408473.1:c.*25G>C NM_001408474.1:c.2001G>C NP_001395403.1:p.Trp667Cys missense NM_001408475.1:c.1998G>C NP_001395404.1:p.Trp666Cys missense NM_001408476.1:c.1998G>C NP_001395405.1:p.Trp666Cys missense NM_001408478.1:c.1992G>C NP_001395407.1:p.Trp664Cys missense NM_001408479.1:c.1992G>C NP_001395408.1:p.Trp664Cys missense NM_001408480.1:c.1992G>C NP_001395409.1:p.Trp664Cys missense NM_001408481.1:c.1989G>C NP_001395410.1:p.Trp663Cys missense NM_001408482.1:c.1989G>C NP_001395411.1:p.Trp663Cys missense NM_001408483.1:c.1989G>C NP_001395412.1:p.Trp663Cys missense NM_001408484.1:c.1989G>C NP_001395413.1:p.Trp663Cys missense NM_001408485.1:c.1989G>C NP_001395414.1:p.Trp663Cys missense NM_001408489.1:c.1989G>C NP_001395418.1:p.Trp663Cys missense NM_001408490.1:c.1989G>C NP_001395419.1:p.Trp663Cys missense NM_001408491.1:c.1989G>C NP_001395420.1:p.Trp663Cys missense NM_001408492.1:c.1986G>C NP_001395421.1:p.Trp662Cys missense NM_001408493.1:c.1986G>C NP_001395422.1:p.Trp662Cys missense NM_001408494.1:c.1962G>C NP_001395423.1:p.Trp654Cys missense NM_001408495.1:c.1956G>C NP_001395424.1:p.Trp652Cys missense NM_001408496.1:c.1938G>C NP_001395425.1:p.Trp646Cys missense NM_001408497.1:c.1938G>C NP_001395426.1:p.Trp646Cys missense NM_001408498.1:c.1938G>C NP_001395427.1:p.Trp646Cys missense NM_001408499.1:c.1938G>C NP_001395428.1:p.Trp646Cys missense NM_001408500.1:c.1938G>C NP_001395429.1:p.Trp646Cys missense NM_001408501.1:c.1938G>C NP_001395430.1:p.Trp646Cys missense NM_001408502.1:c.1935G>C NP_001395431.1:p.Trp645Cys missense NM_001408503.1:c.1935G>C NP_001395432.1:p.Trp645Cys missense NM_001408504.1:c.1935G>C NP_001395433.1:p.Trp645Cys missense NM_001408505.1:c.1932G>C NP_001395434.1:p.Trp644Cys missense NM_001408506.1:c.1875G>C NP_001395435.1:p.Trp625Cys missense NM_001408507.1:c.1872G>C NP_001395436.1:p.Trp624Cys missense NM_001408508.1:c.1863G>C NP_001395437.1:p.Trp621Cys missense NM_001408509.1:c.1860G>C NP_001395438.1:p.Trp620Cys missense NM_001408510.1:c.1821G>C NP_001395439.1:p.Trp607Cys missense NM_001408511.1:c.1818G>C NP_001395440.1:p.Trp606Cys missense NM_001408512.1:c.1698G>C NP_001395441.1:p.Trp566Cys missense NM_001408513.1:c.1671G>C NP_001395442.1:p.Trp557Cys missense NM_001408514.1:c.1275G>C NP_001395443.1:p.Trp425Cys missense NM_007297.4:c.5370G>C NP_009228.2:p.Trp1790Cys missense NM_007298.4:c.2199G>C NP_009229.2:p.Trp733Cys missense NM_007299.4:c.*25G>C 3 prime UTR NM_007300.4:c.5574G>C NP_009231.2:p.Trp1858Cys missense NM_007304.2:c.2199G>C NP_009235.2:p.Trp733Cys missense NR_027676.2:n.5688G>C non-coding transcript variant NC_000017.11:g.43045759C>G NC_000017.10:g.41197776C>G NG_005905.2:g.172225G>C LRG_292:g.172225G>C LRG_292t1:c.5511G>C LRG_292p1:p.Trp1837Cys - Protein change
- W1837C, W1790C, W733C, W1858C, W1540C, W1709C, W1724C, W1753C, W1766C, W1788C, W1789C, W1796C, W1833C, W566C, W689C, W691C, W708C, W731C, W755C, W968C, W1541C, W1726C, W1748C, W1767C, W1795C, W1809C, W1817C, W1818C, W1857C, W1859C, W621C, W662C, W663C, W666C, W693C, W694C, W707C, W709C, W734C, W969C, W1668C, W1683C, W1725C, W1747C, W1770C, W1793C, W1810C, W1832C, W1835C, W645C, W646C, W664C, W695C, W732C, W756C, W1708C, W1710C, W1749C, W1765C, W1768C, W1769C, W1794C, W1811C, W1834C, W1836C, W425C, W557C, W606C, W607C, W620C, W624C, W625C, W644C, W652C, W654C, W667C, W685C, W686C, W687C, W692C, W730C
- Other names
- -
- Canonical SPDI
- NC_000017.11:43045758:C: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.5511G>C, a MISSENSE variant, produced a function score of -2.68, 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 |
12752 | 14513 |
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 (1) |
criteria provided, single submitter
|
Feb 3, 2020 | RCV000483084.3 | |
not provided (1) |
no classification provided
|
- | RCV001078019.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 15, 2023 | RCV001254336.7 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 29, 2022 | RCV001184314.6 |
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
(May 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Breast Center, Key Laboratory of Carcinogenesis and Translational Research
Accession: SCV001430321.1
First in ClinVar: Aug 21, 2020 Last updated: Aug 21, 2020 |
Number of individuals with the variant: 5
Sex: female
Ethnicity/Population group: Chinese
|
|
Pathogenic
(Feb 03, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000570380.4
First in ClinVar: Apr 29, 2017 Last updated: Apr 29, 2017 |
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Also … (more)
Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Also known as 5630G>C; This variant is associated with the following publications: (PMID: 26956035, 22855649, 20516115, 24845084, 30209399, 28781887, 29752822, 30765603, 31124283, 31825140) (less)
|
|
Pathogenic
(Nov 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003856601.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
Comment:
The p.W1837C pathogenic mutation (also known as c.5511G>C), located in coding exon 22 of the BRCA1 gene, results from a G to C substitution at … (more)
The p.W1837C pathogenic mutation (also known as c.5511G>C), located in coding exon 22 of the BRCA1 gene, results from a G to C substitution at nucleotide position 5511. The tryptophan at codon 1837 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been identified in multiple breast cancer patients (Li JY et al. Int J Cancer. 2019 Jan;144:281-289; Wan Q et al. Fam Cancer. 2021 Apr;20:85-95). Multiple functional analyses have found that this nucleotide substitution to leads to a non-functional protein (Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Findlay GM et al. Nature. 2018 Oct;562:217-222; Wan Q et al. Fam Cancer. 2021 Apr;20:85-95). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Pathogenic
(Jan 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001350265.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces tryptophan with cysteine at codon 1837 in the BRCT2 domain of the BRCA1 protein. Computational prediction suggests that this variant may … (more)
This missense variant replaces tryptophan with cysteine at codon 1837 in the BRCT2 domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant has reduced HDR activity, (Ambry data: https://www.ambrygen.com/science/scientific-poster/197/) exhibits severe defects in protease sensitivity, phosphopeptide binding, transcriptional activation, and has been reported to be a loss of function mutation in a haploid cell proliferation assay (PMID: 20516115, 30209399). Functional studies in yeast have shown that this variant exhibits subcellular mislocalization to the cytoplasm, reduced protein stability and a reduced ability to inhibit cell growth (PMID: 27802165). This variant has been reported in individuals affected with ovarian cancer (PMID: 31124283) and breast cancer (Lertwilaiwittaya et al. 2020, https://doi.org/10.21203/rs.3.rs-122156/v1; Color internal data). This variant has also been observed in an individual affected with breast and ovarian cancer, with early-onset breast cancer and ovarian cancer in her two sisters (PMID: 32803532). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Multiple different missense variants occurring at the same amino acid position, p.Trp1837Ser/Cys/Arg/Gly, are reported to be disease-causing, indicating that tryptophan at this position is important for BRCA1 function (ClinVar variation ID: 1065962, 421244, 37680, 853483, 55607). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(May 15, 2023)
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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
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Invitae
Accession: SCV002109539.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp1837 amino acid residue in BRCA1. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp1837 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8968102, 11802209, 15689452, 27741520, 28324225). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 20516115, 27802165, 30209399). 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. ClinVar contains an entry for this variant (Variation ID: 421244). This missense change has been observed in individual(s) with hereditary breast cancer and/or ovarian cancer (PMID: 29752822; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 1837 of the BRCA1 protein (p.Trp1837Cys). (less)
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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: SCV001244041.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.67815028387303
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Germline Functional Evidence
Functional
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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
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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: SCV001244041.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5511G>C, a MISSENSE variant, produced a function score of -2.68, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5511G>C, a MISSENSE variant, produced a function score of -2.68, 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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Clinical phenotypes combined with saturation genome editing identifying the pathogenicity of BRCA1 variants of uncertain significance in breast cancer. | Wan Q | Familial cancer | 2021 | PMID: 32803532 |
Comprehensive genomic profiling of high-grade serous ovarian carcinoma from Chinese patients identifies co-occurring mutations in the Ras/Raf pathway with TP53. | Zhong F | Cancer medicine | 2019 | PMID: 31124283 |
Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
Yeast cells reveal the misfolding and the cellular mislocalization of the human BRCA1 protein. | Thouvenot P | Journal of cell science | 2016 | PMID: 27802165 |
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 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Classification of BRCA1 missense variants of unknown clinical significance. | Phelan CM | Journal of medical genetics | 2005 | PMID: 15689452 |
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 rs80356914 ...
HelpRecord last updated Mar 30, 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.