ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.677G>A (p.Cys226Tyr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(5); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.677G>A (p.Cys226Tyr)
Variation ID: 441363 Accession: VCV000441363.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43094854 (GRCh38) [ NCBI UCSC ] 17: 41246871 (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 Oct 23, 2017 May 1, 2024 Nov 30, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.677G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Cys226Tyr missense NM_001407571.1:c.464G>A NP_001394500.1:p.Cys155Tyr missense NM_001407581.1:c.677G>A NP_001394510.1:p.Cys226Tyr missense NM_001407582.1:c.677G>A NP_001394511.1:p.Cys226Tyr missense NM_001407583.1:c.677G>A NP_001394512.1:p.Cys226Tyr missense NM_001407585.1:c.677G>A NP_001394514.1:p.Cys226Tyr missense NM_001407587.1:c.674G>A NP_001394516.1:p.Cys225Tyr missense NM_001407590.1:c.674G>A NP_001394519.1:p.Cys225Tyr missense NM_001407591.1:c.674G>A NP_001394520.1:p.Cys225Tyr missense NM_001407593.1:c.677G>A NP_001394522.1:p.Cys226Tyr missense NM_001407594.1:c.677G>A NP_001394523.1:p.Cys226Tyr missense NM_001407596.1:c.677G>A NP_001394525.1:p.Cys226Tyr missense NM_001407597.1:c.677G>A NP_001394526.1:p.Cys226Tyr missense NM_001407598.1:c.677G>A NP_001394527.1:p.Cys226Tyr missense NM_001407602.1:c.677G>A NP_001394531.1:p.Cys226Tyr missense NM_001407603.1:c.677G>A NP_001394532.1:p.Cys226Tyr missense NM_001407605.1:c.677G>A NP_001394534.1:p.Cys226Tyr missense NM_001407610.1:c.674G>A NP_001394539.1:p.Cys225Tyr missense NM_001407611.1:c.674G>A NP_001394540.1:p.Cys225Tyr missense NM_001407612.1:c.674G>A NP_001394541.1:p.Cys225Tyr missense NM_001407613.1:c.674G>A NP_001394542.1:p.Cys225Tyr missense NM_001407614.1:c.674G>A NP_001394543.1:p.Cys225Tyr missense NM_001407615.1:c.674G>A NP_001394544.1:p.Cys225Tyr missense NM_001407616.1:c.677G>A NP_001394545.1:p.Cys226Tyr missense NM_001407617.1:c.677G>A NP_001394546.1:p.Cys226Tyr missense NM_001407618.1:c.677G>A NP_001394547.1:p.Cys226Tyr missense NM_001407619.1:c.677G>A NP_001394548.1:p.Cys226Tyr missense NM_001407620.1:c.677G>A NP_001394549.1:p.Cys226Tyr missense NM_001407621.1:c.677G>A NP_001394550.1:p.Cys226Tyr missense NM_001407622.1:c.677G>A NP_001394551.1:p.Cys226Tyr missense NM_001407623.1:c.677G>A NP_001394552.1:p.Cys226Tyr missense NM_001407624.1:c.677G>A NP_001394553.1:p.Cys226Tyr missense NM_001407625.1:c.677G>A NP_001394554.1:p.Cys226Tyr missense NM_001407626.1:c.677G>A NP_001394555.1:p.Cys226Tyr missense NM_001407627.1:c.674G>A NP_001394556.1:p.Cys225Tyr missense NM_001407628.1:c.674G>A NP_001394557.1:p.Cys225Tyr missense NM_001407629.1:c.674G>A NP_001394558.1:p.Cys225Tyr missense NM_001407630.1:c.674G>A NP_001394559.1:p.Cys225Tyr missense NM_001407631.1:c.674G>A NP_001394560.1:p.Cys225Tyr missense NM_001407632.1:c.674G>A NP_001394561.1:p.Cys225Tyr missense NM_001407633.1:c.674G>A NP_001394562.1:p.Cys225Tyr missense NM_001407634.1:c.674G>A NP_001394563.1:p.Cys225Tyr missense NM_001407635.1:c.674G>A NP_001394564.1:p.Cys225Tyr missense NM_001407636.1:c.674G>A NP_001394565.1:p.Cys225Tyr missense NM_001407637.1:c.674G>A NP_001394566.1:p.Cys225Tyr missense NM_001407638.1:c.674G>A NP_001394567.1:p.Cys225Tyr missense NM_001407639.1:c.677G>A NP_001394568.1:p.Cys226Tyr missense NM_001407640.1:c.677G>A NP_001394569.1:p.Cys226Tyr missense NM_001407641.1:c.677G>A NP_001394570.1:p.Cys226Tyr missense NM_001407642.1:c.677G>A NP_001394571.1:p.Cys226Tyr missense NM_001407644.1:c.674G>A NP_001394573.1:p.Cys225Tyr missense NM_001407645.1:c.674G>A NP_001394574.1:p.Cys225Tyr missense NM_001407646.1:c.668G>A NP_001394575.1:p.Cys223Tyr missense NM_001407647.1:c.668G>A NP_001394576.1:p.Cys223Tyr missense NM_001407648.1:c.554G>A NP_001394577.1:p.Cys185Tyr missense NM_001407649.1:c.551G>A NP_001394578.1:p.Cys184Tyr missense NM_001407652.1:c.677G>A NP_001394581.1:p.Cys226Tyr missense NM_001407653.1:c.599G>A NP_001394582.1:p.Cys200Tyr missense NM_001407654.1:c.599G>A NP_001394583.1:p.Cys200Tyr missense NM_001407655.1:c.599G>A NP_001394584.1:p.Cys200Tyr missense NM_001407656.1:c.599G>A NP_001394585.1:p.Cys200Tyr missense NM_001407657.1:c.599G>A NP_001394586.1:p.Cys200Tyr missense NM_001407658.1:c.599G>A NP_001394587.1:p.Cys200Tyr missense NM_001407659.1:c.596G>A NP_001394588.1:p.Cys199Tyr missense NM_001407660.1:c.596G>A NP_001394589.1:p.Cys199Tyr missense NM_001407661.1:c.596G>A NP_001394590.1:p.Cys199Tyr missense NM_001407662.1:c.596G>A NP_001394591.1:p.Cys199Tyr missense NM_001407663.1:c.599G>A NP_001394592.1:p.Cys200Tyr missense NM_001407664.1:c.554G>A NP_001394593.1:p.Cys185Tyr missense NM_001407665.1:c.554G>A NP_001394594.1:p.Cys185Tyr missense NM_001407666.1:c.554G>A NP_001394595.1:p.Cys185Tyr missense NM_001407667.1:c.554G>A NP_001394596.1:p.Cys185Tyr missense NM_001407668.1:c.554G>A NP_001394597.1:p.Cys185Tyr missense NM_001407669.1:c.554G>A NP_001394598.1:p.Cys185Tyr missense NM_001407670.1:c.551G>A NP_001394599.1:p.Cys184Tyr missense NM_001407671.1:c.551G>A NP_001394600.1:p.Cys184Tyr missense NM_001407672.1:c.551G>A NP_001394601.1:p.Cys184Tyr missense NM_001407673.1:c.551G>A NP_001394602.1:p.Cys184Tyr missense NM_001407674.1:c.554G>A NP_001394603.1:p.Cys185Tyr missense NM_001407675.1:c.554G>A NP_001394604.1:p.Cys185Tyr missense NM_001407676.1:c.554G>A NP_001394605.1:p.Cys185Tyr missense NM_001407677.1:c.554G>A NP_001394606.1:p.Cys185Tyr missense NM_001407678.1:c.554G>A NP_001394607.1:p.Cys185Tyr missense NM_001407679.1:c.554G>A NP_001394608.1:p.Cys185Tyr missense NM_001407680.1:c.554G>A NP_001394609.1:p.Cys185Tyr missense NM_001407681.1:c.554G>A NP_001394610.1:p.Cys185Tyr missense NM_001407682.1:c.554G>A NP_001394611.1:p.Cys185Tyr missense NM_001407683.1:c.554G>A NP_001394612.1:p.Cys185Tyr missense NM_001407684.1:c.677G>A NP_001394613.1:p.Cys226Tyr missense NM_001407685.1:c.551G>A NP_001394614.1:p.Cys184Tyr missense NM_001407686.1:c.551G>A NP_001394615.1:p.Cys184Tyr missense NM_001407687.1:c.551G>A NP_001394616.1:p.Cys184Tyr missense NM_001407688.1:c.551G>A NP_001394617.1:p.Cys184Tyr missense NM_001407689.1:c.551G>A NP_001394618.1:p.Cys184Tyr missense NM_001407690.1:c.551G>A NP_001394619.1:p.Cys184Tyr missense NM_001407691.1:c.551G>A NP_001394620.1:p.Cys184Tyr missense NM_001407692.1:c.536G>A NP_001394621.1:p.Cys179Tyr missense NM_001407694.1:c.536G>A NP_001394623.1:p.Cys179Tyr missense NM_001407695.1:c.536G>A NP_001394624.1:p.Cys179Tyr missense NM_001407696.1:c.536G>A NP_001394625.1:p.Cys179Tyr missense NM_001407697.1:c.536G>A NP_001394626.1:p.Cys179Tyr missense NM_001407698.1:c.536G>A NP_001394627.1:p.Cys179Tyr missense NM_001407724.1:c.536G>A NP_001394653.1:p.Cys179Tyr missense NM_001407725.1:c.536G>A NP_001394654.1:p.Cys179Tyr missense NM_001407726.1:c.536G>A NP_001394655.1:p.Cys179Tyr missense NM_001407727.1:c.536G>A NP_001394656.1:p.Cys179Tyr missense NM_001407728.1:c.536G>A NP_001394657.1:p.Cys179Tyr missense NM_001407729.1:c.536G>A NP_001394658.1:p.Cys179Tyr missense NM_001407730.1:c.536G>A NP_001394659.1:p.Cys179Tyr missense NM_001407731.1:c.536G>A NP_001394660.1:p.Cys179Tyr missense NM_001407732.1:c.536G>A NP_001394661.1:p.Cys179Tyr missense NM_001407733.1:c.536G>A NP_001394662.1:p.Cys179Tyr missense NM_001407734.1:c.536G>A NP_001394663.1:p.Cys179Tyr missense NM_001407735.1:c.536G>A NP_001394664.1:p.Cys179Tyr missense NM_001407736.1:c.536G>A NP_001394665.1:p.Cys179Tyr missense NM_001407737.1:c.536G>A NP_001394666.1:p.Cys179Tyr missense NM_001407738.1:c.536G>A NP_001394667.1:p.Cys179Tyr missense NM_001407739.1:c.536G>A NP_001394668.1:p.Cys179Tyr missense NM_001407740.1:c.533G>A NP_001394669.1:p.Cys178Tyr missense NM_001407741.1:c.533G>A NP_001394670.1:p.Cys178Tyr missense NM_001407742.1:c.533G>A NP_001394671.1:p.Cys178Tyr missense NM_001407743.1:c.533G>A NP_001394672.1:p.Cys178Tyr missense NM_001407744.1:c.533G>A NP_001394673.1:p.Cys178Tyr missense NM_001407745.1:c.533G>A NP_001394674.1:p.Cys178Tyr missense NM_001407746.1:c.533G>A NP_001394675.1:p.Cys178Tyr missense NM_001407747.1:c.533G>A NP_001394676.1:p.Cys178Tyr missense NM_001407748.1:c.533G>A NP_001394677.1:p.Cys178Tyr missense NM_001407749.1:c.533G>A NP_001394678.1:p.Cys178Tyr missense NM_001407750.1:c.536G>A NP_001394679.1:p.Cys179Tyr missense NM_001407751.1:c.536G>A NP_001394680.1:p.Cys179Tyr missense NM_001407752.1:c.536G>A NP_001394681.1:p.Cys179Tyr missense NM_001407838.1:c.533G>A NP_001394767.1:p.Cys178Tyr missense NM_001407839.1:c.533G>A NP_001394768.1:p.Cys178Tyr missense NM_001407841.1:c.533G>A NP_001394770.1:p.Cys178Tyr missense NM_001407842.1:c.533G>A NP_001394771.1:p.Cys178Tyr missense NM_001407843.1:c.533G>A NP_001394772.1:p.Cys178Tyr missense NM_001407844.1:c.533G>A NP_001394773.1:p.Cys178Tyr missense NM_001407845.1:c.533G>A NP_001394774.1:p.Cys178Tyr missense NM_001407846.1:c.533G>A NP_001394775.1:p.Cys178Tyr missense NM_001407847.1:c.533G>A NP_001394776.1:p.Cys178Tyr missense NM_001407848.1:c.533G>A NP_001394777.1:p.Cys178Tyr missense NM_001407849.1:c.533G>A NP_001394778.1:p.Cys178Tyr missense NM_001407850.1:c.536G>A NP_001394779.1:p.Cys179Tyr missense NM_001407851.1:c.536G>A NP_001394780.1:p.Cys179Tyr missense NM_001407852.1:c.536G>A NP_001394781.1:p.Cys179Tyr missense NM_001407853.1:c.464G>A NP_001394782.1:p.Cys155Tyr missense NM_001407854.1:c.677G>A NP_001394783.1:p.Cys226Tyr missense NM_001407858.1:c.677G>A NP_001394787.1:p.Cys226Tyr missense NM_001407859.1:c.677G>A NP_001394788.1:p.Cys226Tyr missense NM_001407860.1:c.674G>A NP_001394789.1:p.Cys225Tyr missense NM_001407861.1:c.674G>A NP_001394790.1:p.Cys225Tyr missense NM_001407862.1:c.476G>A NP_001394791.1:p.Cys159Tyr missense NM_001407863.1:c.554G>A NP_001394792.1:p.Cys185Tyr missense NM_001407874.1:c.473G>A NP_001394803.1:p.Cys158Tyr missense NM_001407875.1:c.473G>A NP_001394804.1:p.Cys158Tyr missense NM_001407879.1:c.467G>A NP_001394808.1:p.Cys156Tyr missense NM_001407881.1:c.467G>A NP_001394810.1:p.Cys156Tyr missense NM_001407882.1:c.467G>A NP_001394811.1:p.Cys156Tyr missense NM_001407884.1:c.467G>A NP_001394813.1:p.Cys156Tyr missense NM_001407885.1:c.467G>A NP_001394814.1:p.Cys156Tyr missense NM_001407886.1:c.467G>A NP_001394815.1:p.Cys156Tyr missense NM_001407887.1:c.467G>A NP_001394816.1:p.Cys156Tyr missense NM_001407889.1:c.467G>A NP_001394818.1:p.Cys156Tyr missense NM_001407894.1:c.464G>A NP_001394823.1:p.Cys155Tyr missense NM_001407895.1:c.464G>A NP_001394824.1:p.Cys155Tyr missense NM_001407896.1:c.464G>A NP_001394825.1:p.Cys155Tyr missense NM_001407897.1:c.464G>A NP_001394826.1:p.Cys155Tyr missense NM_001407898.1:c.464G>A NP_001394827.1:p.Cys155Tyr missense NM_001407899.1:c.464G>A NP_001394828.1:p.Cys155Tyr missense NM_001407900.1:c.467G>A NP_001394829.1:p.Cys156Tyr missense NM_001407902.1:c.467G>A NP_001394831.1:p.Cys156Tyr missense NM_001407904.1:c.467G>A NP_001394833.1:p.Cys156Tyr missense NM_001407906.1:c.467G>A NP_001394835.1:p.Cys156Tyr missense NM_001407907.1:c.467G>A NP_001394836.1:p.Cys156Tyr missense NM_001407908.1:c.467G>A NP_001394837.1:p.Cys156Tyr missense NM_001407909.1:c.467G>A NP_001394838.1:p.Cys156Tyr missense NM_001407910.1:c.467G>A NP_001394839.1:p.Cys156Tyr missense NM_001407915.1:c.464G>A NP_001394844.1:p.Cys155Tyr missense NM_001407916.1:c.464G>A NP_001394845.1:p.Cys155Tyr missense NM_001407917.1:c.464G>A NP_001394846.1:p.Cys155Tyr missense NM_001407918.1:c.464G>A NP_001394847.1:p.Cys155Tyr missense NM_001407919.1:c.554G>A NP_001394848.1:p.Cys185Tyr missense NM_001407920.1:c.413G>A NP_001394849.1:p.Cys138Tyr missense NM_001407921.1:c.413G>A NP_001394850.1:p.Cys138Tyr missense NM_001407922.1:c.413G>A NP_001394851.1:p.Cys138Tyr missense NM_001407923.1:c.413G>A NP_001394852.1:p.Cys138Tyr missense NM_001407924.1:c.413G>A NP_001394853.1:p.Cys138Tyr missense NM_001407925.1:c.413G>A NP_001394854.1:p.Cys138Tyr missense NM_001407926.1:c.413G>A NP_001394855.1:p.Cys138Tyr missense NM_001407927.1:c.413G>A NP_001394856.1:p.Cys138Tyr missense NM_001407928.1:c.413G>A NP_001394857.1:p.Cys138Tyr missense NM_001407929.1:c.413G>A NP_001394858.1:p.Cys138Tyr missense NM_001407930.1:c.410G>A NP_001394859.1:p.Cys137Tyr missense NM_001407931.1:c.410G>A NP_001394860.1:p.Cys137Tyr missense NM_001407932.1:c.410G>A NP_001394861.1:p.Cys137Tyr missense NM_001407933.1:c.413G>A NP_001394862.1:p.Cys138Tyr missense NM_001407934.1:c.410G>A NP_001394863.1:p.Cys137Tyr missense NM_001407935.1:c.413G>A NP_001394864.1:p.Cys138Tyr missense NM_001407936.1:c.410G>A NP_001394865.1:p.Cys137Tyr missense NM_001407937.1:c.554G>A NP_001394866.1:p.Cys185Tyr missense NM_001407938.1:c.554G>A NP_001394867.1:p.Cys185Tyr missense NM_001407939.1:c.554G>A NP_001394868.1:p.Cys185Tyr missense NM_001407940.1:c.551G>A NP_001394869.1:p.Cys184Tyr missense NM_001407941.1:c.551G>A NP_001394870.1:p.Cys184Tyr missense NM_001407942.1:c.536G>A NP_001394871.1:p.Cys179Tyr missense NM_001407943.1:c.533G>A NP_001394872.1:p.Cys178Tyr missense NM_001407944.1:c.536G>A NP_001394873.1:p.Cys179Tyr missense NM_001407945.1:c.536G>A NP_001394874.1:p.Cys179Tyr missense NM_001407946.1:c.344G>A NP_001394875.1:p.Cys115Tyr missense NM_001407947.1:c.344G>A NP_001394876.1:p.Cys115Tyr missense NM_001407948.1:c.344G>A NP_001394877.1:p.Cys115Tyr missense NM_001407949.1:c.344G>A NP_001394878.1:p.Cys115Tyr missense NM_001407950.1:c.344G>A NP_001394879.1:p.Cys115Tyr missense NM_001407951.1:c.344G>A NP_001394880.1:p.Cys115Tyr missense NM_001407952.1:c.344G>A NP_001394881.1:p.Cys115Tyr missense NM_001407953.1:c.344G>A NP_001394882.1:p.Cys115Tyr missense NM_001407954.1:c.341G>A NP_001394883.1:p.Cys114Tyr missense NM_001407955.1:c.341G>A NP_001394884.1:p.Cys114Tyr missense NM_001407956.1:c.341G>A NP_001394885.1:p.Cys114Tyr missense NM_001407957.1:c.344G>A NP_001394886.1:p.Cys115Tyr missense NM_001407958.1:c.341G>A NP_001394887.1:p.Cys114Tyr missense NM_001407959.1:c.296G>A NP_001394888.1:p.Cys99Tyr missense NM_001407960.1:c.296G>A NP_001394889.1:p.Cys99Tyr missense NM_001407962.1:c.293G>A NP_001394891.1:p.Cys98Tyr missense NM_001407963.1:c.296G>A NP_001394892.1:p.Cys99Tyr missense NM_001407964.1:c.533G>A NP_001394893.1:p.Cys178Tyr missense NM_001407965.1:c.173G>A NP_001394894.1:p.Cys58Tyr missense NM_001407966.1:c.-212G>A NM_001407967.1:c.-212G>A NM_001407968.1:c.677G>A NP_001394897.1:p.Cys226Tyr missense NM_001407969.1:c.677G>A NP_001394898.1:p.Cys226Tyr missense NM_001407970.1:c.677G>A NP_001394899.1:p.Cys226Tyr missense NM_001407971.1:c.677G>A NP_001394900.1:p.Cys226Tyr missense NM_001407972.1:c.674G>A NP_001394901.1:p.Cys225Tyr missense NM_001407973.1:c.677G>A NP_001394902.1:p.Cys226Tyr missense NM_001407974.1:c.677G>A NP_001394903.1:p.Cys226Tyr missense NM_001407975.1:c.677G>A NP_001394904.1:p.Cys226Tyr missense NM_001407976.1:c.677G>A NP_001394905.1:p.Cys226Tyr missense NM_001407977.1:c.677G>A NP_001394906.1:p.Cys226Tyr missense NM_001407978.1:c.677G>A NP_001394907.1:p.Cys226Tyr missense NM_001407979.1:c.677G>A NP_001394908.1:p.Cys226Tyr missense NM_001407980.1:c.677G>A NP_001394909.1:p.Cys226Tyr missense NM_001407981.1:c.677G>A NP_001394910.1:p.Cys226Tyr missense NM_001407982.1:c.677G>A NP_001394911.1:p.Cys226Tyr missense NM_001407983.1:c.677G>A NP_001394912.1:p.Cys226Tyr missense NM_001407984.1:c.674G>A NP_001394913.1:p.Cys225Tyr missense NM_001407985.1:c.674G>A NP_001394914.1:p.Cys225Tyr missense NM_001407986.1:c.674G>A NP_001394915.1:p.Cys225Tyr missense NM_001407990.1:c.677G>A NP_001394919.1:p.Cys226Tyr missense NM_001407991.1:c.674G>A NP_001394920.1:p.Cys225Tyr missense NM_001407992.1:c.674G>A NP_001394921.1:p.Cys225Tyr missense NM_001407993.1:c.677G>A NP_001394922.1:p.Cys226Tyr missense NM_001408392.1:c.674G>A NP_001395321.1:p.Cys225Tyr missense NM_001408396.1:c.674G>A NP_001395325.1:p.Cys225Tyr missense NM_001408397.1:c.674G>A NP_001395326.1:p.Cys225Tyr missense NM_001408398.1:c.674G>A NP_001395327.1:p.Cys225Tyr missense NM_001408399.1:c.674G>A NP_001395328.1:p.Cys225Tyr missense NM_001408400.1:c.674G>A NP_001395329.1:p.Cys225Tyr missense NM_001408401.1:c.674G>A NP_001395330.1:p.Cys225Tyr missense NM_001408402.1:c.674G>A NP_001395331.1:p.Cys225Tyr missense NM_001408403.1:c.677G>A NP_001395332.1:p.Cys226Tyr missense NM_001408404.1:c.677G>A NP_001395333.1:p.Cys226Tyr missense NM_001408406.1:c.677G>A NP_001395335.1:p.Cys226Tyr missense NM_001408407.1:c.674G>A NP_001395336.1:p.Cys225Tyr missense NM_001408408.1:c.668G>A NP_001395337.1:p.Cys223Tyr missense NM_001408409.1:c.599G>A NP_001395338.1:p.Cys200Tyr missense NM_001408410.1:c.536G>A NP_001395339.1:p.Cys179Tyr missense NM_001408411.1:c.599G>A NP_001395340.1:p.Cys200Tyr missense NM_001408412.1:c.599G>A NP_001395341.1:p.Cys200Tyr missense NM_001408413.1:c.596G>A NP_001395342.1:p.Cys199Tyr missense NM_001408414.1:c.599G>A NP_001395343.1:p.Cys200Tyr missense NM_001408415.1:c.599G>A NP_001395344.1:p.Cys200Tyr missense NM_001408416.1:c.596G>A NP_001395345.1:p.Cys199Tyr missense NM_001408425.1:c.554G>A NP_001395354.1:p.Cys185Tyr missense NM_001408426.1:c.554G>A NP_001395355.1:p.Cys185Tyr missense NM_001408427.1:c.554G>A NP_001395356.1:p.Cys185Tyr missense NM_001408428.1:c.554G>A NP_001395357.1:p.Cys185Tyr missense NM_001408429.1:c.554G>A NP_001395358.1:p.Cys185Tyr missense NM_001408430.1:c.554G>A NP_001395359.1:p.Cys185Tyr missense NM_001408432.1:c.551G>A NP_001395361.1:p.Cys184Tyr missense NM_001408433.1:c.551G>A NP_001395362.1:p.Cys184Tyr missense NM_001408434.1:c.551G>A NP_001395363.1:p.Cys184Tyr missense NM_001408435.1:c.551G>A NP_001395364.1:p.Cys184Tyr missense NM_001408436.1:c.554G>A NP_001395365.1:p.Cys185Tyr missense NM_001408437.1:c.554G>A NP_001395366.1:p.Cys185Tyr missense NM_001408438.1:c.554G>A NP_001395367.1:p.Cys185Tyr missense NM_001408439.1:c.554G>A NP_001395368.1:p.Cys185Tyr missense NM_001408440.1:c.554G>A NP_001395369.1:p.Cys185Tyr missense NM_001408441.1:c.554G>A NP_001395370.1:p.Cys185Tyr missense NM_001408442.1:c.554G>A NP_001395371.1:p.Cys185Tyr missense NM_001408443.1:c.554G>A NP_001395372.1:p.Cys185Tyr missense NM_001408444.1:c.554G>A NP_001395373.1:p.Cys185Tyr missense NM_001408445.1:c.551G>A NP_001395374.1:p.Cys184Tyr missense NM_001408446.1:c.551G>A NP_001395375.1:p.Cys184Tyr missense NM_001408447.1:c.551G>A NP_001395376.1:p.Cys184Tyr missense NM_001408448.1:c.551G>A NP_001395377.1:p.Cys184Tyr missense NM_001408450.1:c.551G>A NP_001395379.1:p.Cys184Tyr missense NM_001408451.1:c.542G>A NP_001395380.1:p.Cys181Tyr missense NM_001408452.1:c.536G>A NP_001395381.1:p.Cys179Tyr missense NM_001408453.1:c.536G>A NP_001395382.1:p.Cys179Tyr missense NM_001408454.1:c.536G>A NP_001395383.1:p.Cys179Tyr missense NM_001408455.1:c.536G>A NP_001395384.1:p.Cys179Tyr missense NM_001408456.1:c.536G>A NP_001395385.1:p.Cys179Tyr missense NM_001408457.1:c.536G>A NP_001395386.1:p.Cys179Tyr missense NM_001408458.1:c.536G>A NP_001395387.1:p.Cys179Tyr missense NM_001408459.1:c.536G>A NP_001395388.1:p.Cys179Tyr missense NM_001408460.1:c.536G>A NP_001395389.1:p.Cys179Tyr missense NM_001408461.1:c.536G>A NP_001395390.1:p.Cys179Tyr missense NM_001408462.1:c.533G>A NP_001395391.1:p.Cys178Tyr missense NM_001408463.1:c.533G>A NP_001395392.1:p.Cys178Tyr missense NM_001408464.1:c.533G>A NP_001395393.1:p.Cys178Tyr missense NM_001408465.1:c.533G>A NP_001395394.1:p.Cys178Tyr missense NM_001408466.1:c.536G>A NP_001395395.1:p.Cys179Tyr missense NM_001408467.1:c.536G>A NP_001395396.1:p.Cys179Tyr missense NM_001408468.1:c.533G>A NP_001395397.1:p.Cys178Tyr missense NM_001408469.1:c.536G>A NP_001395398.1:p.Cys179Tyr missense NM_001408470.1:c.533G>A NP_001395399.1:p.Cys178Tyr missense NM_001408472.1:c.677G>A NP_001395401.1:p.Cys226Tyr missense NM_001408473.1:c.674G>A NP_001395402.1:p.Cys225Tyr missense NM_001408474.1:c.476G>A NP_001395403.1:p.Cys159Tyr missense NM_001408475.1:c.473G>A NP_001395404.1:p.Cys158Tyr missense NM_001408476.1:c.476G>A NP_001395405.1:p.Cys159Tyr missense NM_001408478.1:c.467G>A NP_001395407.1:p.Cys156Tyr missense NM_001408479.1:c.467G>A NP_001395408.1:p.Cys156Tyr missense NM_001408480.1:c.467G>A NP_001395409.1:p.Cys156Tyr missense NM_001408481.1:c.467G>A NP_001395410.1:p.Cys156Tyr missense NM_001408482.1:c.467G>A NP_001395411.1:p.Cys156Tyr missense NM_001408483.1:c.467G>A NP_001395412.1:p.Cys156Tyr missense NM_001408484.1:c.467G>A NP_001395413.1:p.Cys156Tyr missense NM_001408485.1:c.467G>A NP_001395414.1:p.Cys156Tyr missense NM_001408489.1:c.467G>A NP_001395418.1:p.Cys156Tyr missense NM_001408490.1:c.464G>A NP_001395419.1:p.Cys155Tyr missense NM_001408491.1:c.464G>A NP_001395420.1:p.Cys155Tyr missense NM_001408492.1:c.467G>A NP_001395421.1:p.Cys156Tyr missense NM_001408493.1:c.464G>A NP_001395422.1:p.Cys155Tyr missense NM_001408496.1:c.413G>A NP_001395425.1:p.Cys138Tyr missense NM_001408497.1:c.413G>A NP_001395426.1:p.Cys138Tyr missense NM_001408498.1:c.413G>A NP_001395427.1:p.Cys138Tyr missense NM_001408499.1:c.413G>A NP_001395428.1:p.Cys138Tyr missense NM_001408500.1:c.413G>A NP_001395429.1:p.Cys138Tyr missense NM_001408501.1:c.413G>A NP_001395430.1:p.Cys138Tyr missense NM_001408502.1:c.344G>A NP_001395431.1:p.Cys115Tyr missense NM_001408503.1:c.410G>A NP_001395432.1:p.Cys137Tyr missense NM_001408504.1:c.410G>A NP_001395433.1:p.Cys137Tyr missense NM_001408505.1:c.410G>A NP_001395434.1:p.Cys137Tyr missense NM_001408508.1:c.341G>A NP_001395437.1:p.Cys114Tyr missense NM_001408509.1:c.341G>A NP_001395438.1:p.Cys114Tyr missense NM_001408510.1:c.296G>A NP_001395439.1:p.Cys99Tyr missense NM_001408512.1:c.173G>A NP_001395441.1:p.Cys58Tyr missense NM_001408513.1:c.467G>A NP_001395442.1:p.Cys156Tyr missense NM_001408514.1:c.467G>A NP_001395443.1:p.Cys156Tyr missense NM_007297.4:c.536G>A NP_009228.2:p.Cys179Tyr missense NM_007298.4:c.677G>A NP_009229.2:p.Cys226Tyr missense NM_007299.4:c.677G>A NP_009230.2:p.Cys226Tyr missense NM_007300.4:c.677G>A NP_009231.2:p.Cys226Tyr missense NM_007304.2:c.677G>A NP_009235.2:p.Cys226Tyr missense NR_027676.2:n.854G>A non-coding transcript variant NC_000017.11:g.43094854C>T NC_000017.10:g.41246871C>T NG_005905.2:g.123130G>A LRG_292:g.123130G>A LRG_292t1:c.677G>A LRG_292p1:p.Cys226Tyr - Protein change
- C226Y, C179Y, C115Y, C137Y, C156Y, C159Y, C184Y, C199Y, C155Y, C158Y, C178Y, C58Y, C98Y, C181Y, C185Y, C99Y, C114Y, C138Y, C200Y, C223Y, C225Y
- Other names
- -
- Canonical SPDI
- NC_000017.11:43094853:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
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 |
12887 | 14672 |
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Mar 23, 2023 | RCV000509844.13 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Sep 17, 2021 | RCV001059852.7 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Aug 15, 2023 | RCV003321640.2 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Nov 30, 2023 | RCV004003569.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Uncertain significance
(Jun 12, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000910118.2
First in ClinVar: May 20, 2019 Last updated: Jun 22, 2020 |
|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003848018.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
Uncertain significance
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004026807.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
|
Uncertain significance
(Sep 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001224502.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 226 of the BRCA1 protein (p.Cys226Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. (less)
|
|
Uncertain Significance
(Nov 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004818425.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 1
|
|
Uncertain significance
(Sep 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000607944.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The p.C226Y variant (also known as c.677G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.C226Y variant (also known as c.677G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 677. The cysteine at codon 226 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
LOVD v.2.0: the next generation in gene variant databases. | Fokkema IF | Human mutation | 2011 | PMID: 21520333 |
Text-mined citations for rs1376262238 ...
HelpRecord last updated Jun 02, 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.