ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1686T>G (p.Ile562Met)
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(4); 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.1686T>G (p.Ile562Met)
Variation ID: 441443 Accession: VCV000441443.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093845 (GRCh38) [ NCBI UCSC ] 17: 41245862 (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 Aug 15, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.1686T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ile562Met missense NM_001407571.1:c.1473T>G NP_001394500.1:p.Ile491Met missense NM_001407581.1:c.1686T>G NP_001394510.1:p.Ile562Met missense NM_001407582.1:c.1686T>G NP_001394511.1:p.Ile562Met missense NM_001407583.1:c.1686T>G NP_001394512.1:p.Ile562Met missense NM_001407585.1:c.1686T>G NP_001394514.1:p.Ile562Met missense NM_001407587.1:c.1683T>G NP_001394516.1:p.Ile561Met missense NM_001407590.1:c.1683T>G NP_001394519.1:p.Ile561Met missense NM_001407591.1:c.1683T>G NP_001394520.1:p.Ile561Met missense NM_001407593.1:c.1686T>G NP_001394522.1:p.Ile562Met missense NM_001407594.1:c.1686T>G NP_001394523.1:p.Ile562Met missense NM_001407596.1:c.1686T>G NP_001394525.1:p.Ile562Met missense NM_001407597.1:c.1686T>G NP_001394526.1:p.Ile562Met missense NM_001407598.1:c.1686T>G NP_001394527.1:p.Ile562Met missense NM_001407602.1:c.1686T>G NP_001394531.1:p.Ile562Met missense NM_001407603.1:c.1686T>G NP_001394532.1:p.Ile562Met missense NM_001407605.1:c.1686T>G NP_001394534.1:p.Ile562Met missense NM_001407610.1:c.1683T>G NP_001394539.1:p.Ile561Met missense NM_001407611.1:c.1683T>G NP_001394540.1:p.Ile561Met missense NM_001407612.1:c.1683T>G NP_001394541.1:p.Ile561Met missense NM_001407613.1:c.1683T>G NP_001394542.1:p.Ile561Met missense NM_001407614.1:c.1683T>G NP_001394543.1:p.Ile561Met missense NM_001407615.1:c.1683T>G NP_001394544.1:p.Ile561Met missense NM_001407616.1:c.1686T>G NP_001394545.1:p.Ile562Met missense NM_001407617.1:c.1686T>G NP_001394546.1:p.Ile562Met missense NM_001407618.1:c.1686T>G NP_001394547.1:p.Ile562Met missense NM_001407619.1:c.1686T>G NP_001394548.1:p.Ile562Met missense NM_001407620.1:c.1686T>G NP_001394549.1:p.Ile562Met missense NM_001407621.1:c.1686T>G NP_001394550.1:p.Ile562Met missense NM_001407622.1:c.1686T>G NP_001394551.1:p.Ile562Met missense NM_001407623.1:c.1686T>G NP_001394552.1:p.Ile562Met missense NM_001407624.1:c.1686T>G NP_001394553.1:p.Ile562Met missense NM_001407625.1:c.1686T>G NP_001394554.1:p.Ile562Met missense NM_001407626.1:c.1686T>G NP_001394555.1:p.Ile562Met missense NM_001407627.1:c.1683T>G NP_001394556.1:p.Ile561Met missense NM_001407628.1:c.1683T>G NP_001394557.1:p.Ile561Met missense NM_001407629.1:c.1683T>G NP_001394558.1:p.Ile561Met missense NM_001407630.1:c.1683T>G NP_001394559.1:p.Ile561Met missense NM_001407631.1:c.1683T>G NP_001394560.1:p.Ile561Met missense NM_001407632.1:c.1683T>G NP_001394561.1:p.Ile561Met missense NM_001407633.1:c.1683T>G NP_001394562.1:p.Ile561Met missense NM_001407634.1:c.1683T>G NP_001394563.1:p.Ile561Met missense NM_001407635.1:c.1683T>G NP_001394564.1:p.Ile561Met missense NM_001407636.1:c.1683T>G NP_001394565.1:p.Ile561Met missense NM_001407637.1:c.1683T>G NP_001394566.1:p.Ile561Met missense NM_001407638.1:c.1683T>G NP_001394567.1:p.Ile561Met missense NM_001407639.1:c.1686T>G NP_001394568.1:p.Ile562Met missense NM_001407640.1:c.1686T>G NP_001394569.1:p.Ile562Met missense NM_001407641.1:c.1686T>G NP_001394570.1:p.Ile562Met missense NM_001407642.1:c.1686T>G NP_001394571.1:p.Ile562Met missense NM_001407644.1:c.1683T>G NP_001394573.1:p.Ile561Met missense NM_001407645.1:c.1683T>G NP_001394574.1:p.Ile561Met missense NM_001407646.1:c.1677T>G NP_001394575.1:p.Ile559Met missense NM_001407647.1:c.1677T>G NP_001394576.1:p.Ile559Met missense NM_001407648.1:c.1563T>G NP_001394577.1:p.Ile521Met missense NM_001407649.1:c.1560T>G NP_001394578.1:p.Ile520Met missense NM_001407652.1:c.1686T>G NP_001394581.1:p.Ile562Met missense NM_001407653.1:c.1608T>G NP_001394582.1:p.Ile536Met missense NM_001407654.1:c.1608T>G NP_001394583.1:p.Ile536Met missense NM_001407655.1:c.1608T>G NP_001394584.1:p.Ile536Met missense NM_001407656.1:c.1608T>G NP_001394585.1:p.Ile536Met missense NM_001407657.1:c.1608T>G NP_001394586.1:p.Ile536Met missense NM_001407658.1:c.1608T>G NP_001394587.1:p.Ile536Met missense NM_001407659.1:c.1605T>G NP_001394588.1:p.Ile535Met missense NM_001407660.1:c.1605T>G NP_001394589.1:p.Ile535Met missense NM_001407661.1:c.1605T>G NP_001394590.1:p.Ile535Met missense NM_001407662.1:c.1605T>G NP_001394591.1:p.Ile535Met missense NM_001407663.1:c.1608T>G NP_001394592.1:p.Ile536Met missense NM_001407664.1:c.1563T>G NP_001394593.1:p.Ile521Met missense NM_001407665.1:c.1563T>G NP_001394594.1:p.Ile521Met missense NM_001407666.1:c.1563T>G NP_001394595.1:p.Ile521Met missense NM_001407667.1:c.1563T>G NP_001394596.1:p.Ile521Met missense NM_001407668.1:c.1563T>G NP_001394597.1:p.Ile521Met missense NM_001407669.1:c.1563T>G NP_001394598.1:p.Ile521Met missense NM_001407670.1:c.1560T>G NP_001394599.1:p.Ile520Met missense NM_001407671.1:c.1560T>G NP_001394600.1:p.Ile520Met missense NM_001407672.1:c.1560T>G NP_001394601.1:p.Ile520Met missense NM_001407673.1:c.1560T>G NP_001394602.1:p.Ile520Met missense NM_001407674.1:c.1563T>G NP_001394603.1:p.Ile521Met missense NM_001407675.1:c.1563T>G NP_001394604.1:p.Ile521Met missense NM_001407676.1:c.1563T>G NP_001394605.1:p.Ile521Met missense NM_001407677.1:c.1563T>G NP_001394606.1:p.Ile521Met missense NM_001407678.1:c.1563T>G NP_001394607.1:p.Ile521Met missense NM_001407679.1:c.1563T>G NP_001394608.1:p.Ile521Met missense NM_001407680.1:c.1563T>G NP_001394609.1:p.Ile521Met missense NM_001407681.1:c.1563T>G NP_001394610.1:p.Ile521Met missense NM_001407682.1:c.1563T>G NP_001394611.1:p.Ile521Met missense NM_001407683.1:c.1563T>G NP_001394612.1:p.Ile521Met missense NM_001407684.1:c.1686T>G NP_001394613.1:p.Ile562Met missense NM_001407685.1:c.1560T>G NP_001394614.1:p.Ile520Met missense NM_001407686.1:c.1560T>G NP_001394615.1:p.Ile520Met missense NM_001407687.1:c.1560T>G NP_001394616.1:p.Ile520Met missense NM_001407688.1:c.1560T>G NP_001394617.1:p.Ile520Met missense NM_001407689.1:c.1560T>G NP_001394618.1:p.Ile520Met missense NM_001407690.1:c.1560T>G NP_001394619.1:p.Ile520Met missense NM_001407691.1:c.1560T>G NP_001394620.1:p.Ile520Met missense NM_001407692.1:c.1545T>G NP_001394621.1:p.Ile515Met missense NM_001407694.1:c.1545T>G NP_001394623.1:p.Ile515Met missense NM_001407695.1:c.1545T>G NP_001394624.1:p.Ile515Met missense NM_001407696.1:c.1545T>G NP_001394625.1:p.Ile515Met missense NM_001407697.1:c.1545T>G NP_001394626.1:p.Ile515Met missense NM_001407698.1:c.1545T>G NP_001394627.1:p.Ile515Met missense NM_001407724.1:c.1545T>G NP_001394653.1:p.Ile515Met missense NM_001407725.1:c.1545T>G NP_001394654.1:p.Ile515Met missense NM_001407726.1:c.1545T>G NP_001394655.1:p.Ile515Met missense NM_001407727.1:c.1545T>G NP_001394656.1:p.Ile515Met missense NM_001407728.1:c.1545T>G NP_001394657.1:p.Ile515Met missense NM_001407729.1:c.1545T>G NP_001394658.1:p.Ile515Met missense NM_001407730.1:c.1545T>G NP_001394659.1:p.Ile515Met missense NM_001407731.1:c.1545T>G NP_001394660.1:p.Ile515Met missense NM_001407732.1:c.1545T>G NP_001394661.1:p.Ile515Met missense NM_001407733.1:c.1545T>G NP_001394662.1:p.Ile515Met missense NM_001407734.1:c.1545T>G NP_001394663.1:p.Ile515Met missense NM_001407735.1:c.1545T>G NP_001394664.1:p.Ile515Met missense NM_001407736.1:c.1545T>G NP_001394665.1:p.Ile515Met missense NM_001407737.1:c.1545T>G NP_001394666.1:p.Ile515Met missense NM_001407738.1:c.1545T>G NP_001394667.1:p.Ile515Met missense NM_001407739.1:c.1545T>G NP_001394668.1:p.Ile515Met missense NM_001407740.1:c.1542T>G NP_001394669.1:p.Ile514Met missense NM_001407741.1:c.1542T>G NP_001394670.1:p.Ile514Met missense NM_001407742.1:c.1542T>G NP_001394671.1:p.Ile514Met missense NM_001407743.1:c.1542T>G NP_001394672.1:p.Ile514Met missense NM_001407744.1:c.1542T>G NP_001394673.1:p.Ile514Met missense NM_001407745.1:c.1542T>G NP_001394674.1:p.Ile514Met missense NM_001407746.1:c.1542T>G NP_001394675.1:p.Ile514Met missense NM_001407747.1:c.1542T>G NP_001394676.1:p.Ile514Met missense NM_001407748.1:c.1542T>G NP_001394677.1:p.Ile514Met missense NM_001407749.1:c.1542T>G NP_001394678.1:p.Ile514Met missense NM_001407750.1:c.1545T>G NP_001394679.1:p.Ile515Met missense NM_001407751.1:c.1545T>G NP_001394680.1:p.Ile515Met missense NM_001407752.1:c.1545T>G NP_001394681.1:p.Ile515Met missense NM_001407838.1:c.1542T>G NP_001394767.1:p.Ile514Met missense NM_001407839.1:c.1542T>G NP_001394768.1:p.Ile514Met missense NM_001407841.1:c.1542T>G NP_001394770.1:p.Ile514Met missense NM_001407842.1:c.1542T>G NP_001394771.1:p.Ile514Met missense NM_001407843.1:c.1542T>G NP_001394772.1:p.Ile514Met missense NM_001407844.1:c.1542T>G NP_001394773.1:p.Ile514Met missense NM_001407845.1:c.1542T>G NP_001394774.1:p.Ile514Met missense NM_001407846.1:c.1542T>G NP_001394775.1:p.Ile514Met missense NM_001407847.1:c.1542T>G NP_001394776.1:p.Ile514Met missense NM_001407848.1:c.1542T>G NP_001394777.1:p.Ile514Met missense NM_001407849.1:c.1542T>G NP_001394778.1:p.Ile514Met missense NM_001407850.1:c.1545T>G NP_001394779.1:p.Ile515Met missense NM_001407851.1:c.1545T>G NP_001394780.1:p.Ile515Met missense NM_001407852.1:c.1545T>G NP_001394781.1:p.Ile515Met missense NM_001407853.1:c.1473T>G NP_001394782.1:p.Ile491Met missense NM_001407854.1:c.1686T>G NP_001394783.1:p.Ile562Met missense NM_001407858.1:c.1686T>G NP_001394787.1:p.Ile562Met missense NM_001407859.1:c.1686T>G NP_001394788.1:p.Ile562Met missense NM_001407860.1:c.1683T>G NP_001394789.1:p.Ile561Met missense NM_001407861.1:c.1683T>G NP_001394790.1:p.Ile561Met missense NM_001407862.1:c.1485T>G NP_001394791.1:p.Ile495Met missense NM_001407863.1:c.1563T>G NP_001394792.1:p.Ile521Met missense NM_001407874.1:c.1482T>G NP_001394803.1:p.Ile494Met missense NM_001407875.1:c.1482T>G NP_001394804.1:p.Ile494Met missense NM_001407879.1:c.1476T>G NP_001394808.1:p.Ile492Met missense NM_001407881.1:c.1476T>G NP_001394810.1:p.Ile492Met missense NM_001407882.1:c.1476T>G NP_001394811.1:p.Ile492Met missense NM_001407884.1:c.1476T>G NP_001394813.1:p.Ile492Met missense NM_001407885.1:c.1476T>G NP_001394814.1:p.Ile492Met missense NM_001407886.1:c.1476T>G NP_001394815.1:p.Ile492Met missense NM_001407887.1:c.1476T>G NP_001394816.1:p.Ile492Met missense NM_001407889.1:c.1476T>G NP_001394818.1:p.Ile492Met missense NM_001407894.1:c.1473T>G NP_001394823.1:p.Ile491Met missense NM_001407895.1:c.1473T>G NP_001394824.1:p.Ile491Met missense NM_001407896.1:c.1473T>G NP_001394825.1:p.Ile491Met missense NM_001407897.1:c.1473T>G NP_001394826.1:p.Ile491Met missense NM_001407898.1:c.1473T>G NP_001394827.1:p.Ile491Met missense NM_001407899.1:c.1473T>G NP_001394828.1:p.Ile491Met missense NM_001407900.1:c.1476T>G NP_001394829.1:p.Ile492Met missense NM_001407902.1:c.1476T>G NP_001394831.1:p.Ile492Met missense NM_001407904.1:c.1476T>G NP_001394833.1:p.Ile492Met missense NM_001407906.1:c.1476T>G NP_001394835.1:p.Ile492Met missense NM_001407907.1:c.1476T>G NP_001394836.1:p.Ile492Met missense NM_001407908.1:c.1476T>G NP_001394837.1:p.Ile492Met missense NM_001407909.1:c.1476T>G NP_001394838.1:p.Ile492Met missense NM_001407910.1:c.1476T>G NP_001394839.1:p.Ile492Met missense NM_001407915.1:c.1473T>G NP_001394844.1:p.Ile491Met missense NM_001407916.1:c.1473T>G NP_001394845.1:p.Ile491Met missense NM_001407917.1:c.1473T>G NP_001394846.1:p.Ile491Met missense NM_001407918.1:c.1473T>G NP_001394847.1:p.Ile491Met missense NM_001407919.1:c.1563T>G NP_001394848.1:p.Ile521Met missense NM_001407920.1:c.1422T>G NP_001394849.1:p.Ile474Met missense NM_001407921.1:c.1422T>G NP_001394850.1:p.Ile474Met missense NM_001407922.1:c.1422T>G NP_001394851.1:p.Ile474Met missense NM_001407923.1:c.1422T>G NP_001394852.1:p.Ile474Met missense NM_001407924.1:c.1422T>G NP_001394853.1:p.Ile474Met missense NM_001407925.1:c.1422T>G NP_001394854.1:p.Ile474Met missense NM_001407926.1:c.1422T>G NP_001394855.1:p.Ile474Met missense NM_001407927.1:c.1422T>G NP_001394856.1:p.Ile474Met missense NM_001407928.1:c.1422T>G NP_001394857.1:p.Ile474Met missense NM_001407929.1:c.1422T>G NP_001394858.1:p.Ile474Met missense NM_001407930.1:c.1419T>G NP_001394859.1:p.Ile473Met missense NM_001407931.1:c.1419T>G NP_001394860.1:p.Ile473Met missense NM_001407932.1:c.1419T>G NP_001394861.1:p.Ile473Met missense NM_001407933.1:c.1422T>G NP_001394862.1:p.Ile474Met missense NM_001407934.1:c.1419T>G NP_001394863.1:p.Ile473Met missense NM_001407935.1:c.1422T>G NP_001394864.1:p.Ile474Met missense NM_001407936.1:c.1419T>G NP_001394865.1:p.Ile473Met missense NM_001407937.1:c.1563T>G NP_001394866.1:p.Ile521Met missense NM_001407938.1:c.1563T>G NP_001394867.1:p.Ile521Met missense NM_001407939.1:c.1563T>G NP_001394868.1:p.Ile521Met missense NM_001407940.1:c.1560T>G NP_001394869.1:p.Ile520Met missense NM_001407941.1:c.1560T>G NP_001394870.1:p.Ile520Met missense NM_001407942.1:c.1545T>G NP_001394871.1:p.Ile515Met missense NM_001407943.1:c.1542T>G NP_001394872.1:p.Ile514Met missense NM_001407944.1:c.1545T>G NP_001394873.1:p.Ile515Met missense NM_001407945.1:c.1545T>G NP_001394874.1:p.Ile515Met missense NM_001407946.1:c.1353T>G NP_001394875.1:p.Ile451Met missense NM_001407947.1:c.1353T>G NP_001394876.1:p.Ile451Met missense NM_001407948.1:c.1353T>G NP_001394877.1:p.Ile451Met missense NM_001407949.1:c.1353T>G NP_001394878.1:p.Ile451Met missense NM_001407950.1:c.1353T>G NP_001394879.1:p.Ile451Met missense NM_001407951.1:c.1353T>G NP_001394880.1:p.Ile451Met missense NM_001407952.1:c.1353T>G NP_001394881.1:p.Ile451Met missense NM_001407953.1:c.1353T>G NP_001394882.1:p.Ile451Met missense NM_001407954.1:c.1350T>G NP_001394883.1:p.Ile450Met missense NM_001407955.1:c.1350T>G NP_001394884.1:p.Ile450Met missense NM_001407956.1:c.1350T>G NP_001394885.1:p.Ile450Met missense NM_001407957.1:c.1353T>G NP_001394886.1:p.Ile451Met missense NM_001407958.1:c.1350T>G NP_001394887.1:p.Ile450Met missense NM_001407959.1:c.1305T>G NP_001394888.1:p.Ile435Met missense NM_001407960.1:c.1305T>G NP_001394889.1:p.Ile435Met missense NM_001407962.1:c.1302T>G NP_001394891.1:p.Ile434Met missense NM_001407963.1:c.1305T>G NP_001394892.1:p.Ile435Met missense NM_001407964.1:c.1542T>G NP_001394893.1:p.Ile514Met missense NM_001407965.1:c.1182T>G NP_001394894.1:p.Ile394Met missense NM_001407966.1:c.798T>G NP_001394895.1:p.Ile266Met missense NM_001407967.1:c.798T>G NP_001394896.1:p.Ile266Met missense NM_001407968.1:c.787+899T>G intron variant NM_001407969.1:c.787+899T>G intron variant NM_001407970.1:c.787+899T>G intron variant NM_001407971.1:c.787+899T>G intron variant NM_001407972.1:c.784+899T>G intron variant NM_001407973.1:c.787+899T>G intron variant NM_001407974.1:c.787+899T>G intron variant NM_001407975.1:c.787+899T>G intron variant NM_001407976.1:c.787+899T>G intron variant NM_001407977.1:c.787+899T>G intron variant NM_001407978.1:c.787+899T>G intron variant NM_001407979.1:c.787+899T>G intron variant NM_001407980.1:c.787+899T>G intron variant NM_001407981.1:c.787+899T>G intron variant NM_001407982.1:c.787+899T>G intron variant NM_001407983.1:c.787+899T>G intron variant NM_001407984.1:c.784+899T>G intron variant NM_001407985.1:c.784+899T>G intron variant NM_001407986.1:c.784+899T>G intron variant NM_001407990.1:c.787+899T>G intron variant NM_001407991.1:c.784+899T>G intron variant NM_001407992.1:c.784+899T>G intron variant NM_001407993.1:c.787+899T>G intron variant NM_001408392.1:c.784+899T>G intron variant NM_001408396.1:c.784+899T>G intron variant NM_001408397.1:c.784+899T>G intron variant NM_001408398.1:c.784+899T>G intron variant NM_001408399.1:c.784+899T>G intron variant NM_001408400.1:c.784+899T>G intron variant NM_001408401.1:c.784+899T>G intron variant NM_001408402.1:c.784+899T>G intron variant NM_001408403.1:c.787+899T>G intron variant NM_001408404.1:c.787+899T>G intron variant NM_001408406.1:c.790+896T>G intron variant NM_001408407.1:c.784+899T>G intron variant NM_001408408.1:c.778+899T>G intron variant NM_001408409.1:c.709+899T>G intron variant NM_001408410.1:c.646+899T>G intron variant NM_001408411.1:c.709+899T>G intron variant NM_001408412.1:c.709+899T>G intron variant NM_001408413.1:c.706+899T>G intron variant NM_001408414.1:c.709+899T>G intron variant NM_001408415.1:c.709+899T>G intron variant NM_001408416.1:c.706+899T>G intron variant NM_001408418.1:c.670+2001T>G intron variant NM_001408419.1:c.670+2001T>G intron variant NM_001408420.1:c.670+2001T>G intron variant NM_001408421.1:c.667+2001T>G intron variant NM_001408422.1:c.670+2001T>G intron variant NM_001408423.1:c.670+2001T>G intron variant NM_001408424.1:c.667+2001T>G intron variant NM_001408425.1:c.664+899T>G intron variant NM_001408426.1:c.664+899T>G intron variant NM_001408427.1:c.664+899T>G intron variant NM_001408428.1:c.664+899T>G intron variant NM_001408429.1:c.664+899T>G intron variant NM_001408430.1:c.664+899T>G intron variant NM_001408431.1:c.667+2001T>G intron variant NM_001408432.1:c.661+899T>G intron variant NM_001408433.1:c.661+899T>G intron variant NM_001408434.1:c.661+899T>G intron variant NM_001408435.1:c.661+899T>G intron variant NM_001408436.1:c.664+899T>G intron variant NM_001408437.1:c.664+899T>G intron variant NM_001408438.1:c.664+899T>G intron variant NM_001408439.1:c.664+899T>G intron variant NM_001408440.1:c.664+899T>G intron variant NM_001408441.1:c.664+899T>G intron variant NM_001408442.1:c.664+899T>G intron variant NM_001408443.1:c.664+899T>G intron variant NM_001408444.1:c.664+899T>G intron variant NM_001408445.1:c.661+899T>G intron variant NM_001408446.1:c.661+899T>G intron variant NM_001408447.1:c.661+899T>G intron variant NM_001408448.1:c.661+899T>G intron variant NM_001408450.1:c.661+899T>G intron variant NM_001408451.1:c.652+899T>G intron variant NM_001408452.1:c.646+899T>G intron variant NM_001408453.1:c.646+899T>G intron variant NM_001408454.1:c.646+899T>G intron variant NM_001408455.1:c.646+899T>G intron variant NM_001408456.1:c.646+899T>G intron variant NM_001408457.1:c.646+899T>G intron variant NM_001408458.1:c.646+899T>G intron variant NM_001408459.1:c.646+899T>G intron variant NM_001408460.1:c.646+899T>G intron variant NM_001408461.1:c.646+899T>G intron variant NM_001408462.1:c.643+899T>G intron variant NM_001408463.1:c.643+899T>G intron variant NM_001408464.1:c.643+899T>G intron variant NM_001408465.1:c.643+899T>G intron variant NM_001408466.1:c.646+899T>G intron variant NM_001408467.1:c.646+899T>G intron variant NM_001408468.1:c.643+899T>G intron variant NM_001408469.1:c.646+899T>G intron variant NM_001408470.1:c.643+899T>G intron variant NM_001408472.1:c.787+899T>G intron variant NM_001408473.1:c.784+899T>G intron variant NM_001408474.1:c.586+899T>G intron variant NM_001408475.1:c.583+899T>G intron variant NM_001408476.1:c.586+899T>G intron variant NM_001408478.1:c.577+899T>G intron variant NM_001408479.1:c.577+899T>G intron variant NM_001408480.1:c.577+899T>G intron variant NM_001408481.1:c.577+899T>G intron variant NM_001408482.1:c.577+899T>G intron variant NM_001408483.1:c.577+899T>G intron variant NM_001408484.1:c.577+899T>G intron variant NM_001408485.1:c.577+899T>G intron variant NM_001408489.1:c.577+899T>G intron variant NM_001408490.1:c.574+899T>G intron variant NM_001408491.1:c.574+899T>G intron variant NM_001408492.1:c.577+899T>G intron variant NM_001408493.1:c.574+899T>G intron variant NM_001408494.1:c.548-2813T>G intron variant NM_001408495.1:c.545-2813T>G intron variant NM_001408496.1:c.523+899T>G intron variant NM_001408497.1:c.523+899T>G intron variant NM_001408498.1:c.523+899T>G intron variant NM_001408499.1:c.523+899T>G intron variant NM_001408500.1:c.523+899T>G intron variant NM_001408501.1:c.523+899T>G intron variant NM_001408502.1:c.454+899T>G intron variant NM_001408503.1:c.520+899T>G intron variant NM_001408504.1:c.520+899T>G intron variant NM_001408505.1:c.520+899T>G intron variant NM_001408506.1:c.460+2001T>G intron variant NM_001408507.1:c.460+2001T>G intron variant NM_001408508.1:c.451+899T>G intron variant NM_001408509.1:c.451+899T>G intron variant NM_001408510.1:c.406+899T>G intron variant NM_001408511.1:c.404-2813T>G intron variant NM_001408512.1:c.283+899T>G intron variant NM_001408513.1:c.577+899T>G intron variant NM_001408514.1:c.577+899T>G intron variant NM_007297.4:c.1545T>G NP_009228.2:p.Ile515Met missense NM_007298.4:c.787+899T>G intron variant NM_007299.4:c.787+899T>G intron variant NM_007300.4:c.1686T>G NP_009231.2:p.Ile562Met missense NR_027676.1:n.1822T>G NC_000017.11:g.43093845A>C NC_000017.10:g.41245862A>C NG_005905.2:g.124139T>G LRG_292:g.124139T>G LRG_292t1:c.1686T>G LRG_292p1:p.Ile562Met - Protein change
- I562M, I515M, I266M, I434M, I435M, I495M, I520M, I521M, I394M, I450M, I474M, I492M, I535M, I561M, I494M, I514M, I536M, I559M, I451M, I473M, I491M
- Other names
- -
- Canonical SPDI
- NC_000017.11:43093844:A:C
-
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.
Trans-Omics for Precision Medicine (TOPMed) 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 | ||
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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. |
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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13037 | 14843 |
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. |
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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Mar 23, 2023 | RCV000510061.8 | |
Uncertain significance (1) |
criteria provided, single submitter
|
May 11, 2023 | RCV001049594.5 | |
Uncertain significance (1) |
criteria provided, single submitter
|
May 23, 2021 | RCV001527021.2 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Aug 15, 2023 | RCV004003578.2 |
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. |
|
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Uncertain significance
(May 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001737842.1
First in ClinVar: Jun 23, 2021 Last updated: Jun 23, 2021 |
Comment:
Variant summary: BRCA1 c.1686T>G (p.Ile562Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign … (more)
Variant summary: BRCA1 c.1686T>G (p.Ile562Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250426 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1686T>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
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Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003851117.1
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).
|
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Uncertain significance
(May 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001213651.4
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 562 of the BRCA1 protein (p.Ile562Met). … (more)
This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 562 of the BRCA1 protein (p.Ile562Met). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 441443). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. (less)
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Uncertain Significance
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004818299.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces isoleucine with methionine at codon 562 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces isoleucine with methionine at codon 562 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Jul 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000608114.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The p.I562M variant (also known as c.1686T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide … (more)
The p.I562M variant (also known as c.1686T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 1686. The isoleucine at codon 562 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 |
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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 |
Text-mined citations for rs1268133978 ...
HelpRecord last updated Oct 08, 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.