Variant summary: BRCA1 c.5339T>C (p.Leu1780Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251430 control chromosomes. c.5339T>C has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. These data indicate that the variant is very likely to be associated with disease. At least one functional study reports experimental evidence evaluating an impact on protein function and showed damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5339T>C (p.Leu1780Pro)
Germline
Classification
Help
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.
(12)
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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.
Pathogenic/Likely pathogenic
12
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5339T>C (p.Leu1780Pro)
Variation ID: 55541 Accession: VCV000055541.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43049188 (GRCh38) [ NCBI UCSC ] 17: 41201205 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Oct 13, 2024 Jan 2, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5339T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu1780Pro missense NM_001407571.1:c.5126T>C NP_001394500.1:p.Leu1709Pro missense NM_001407581.1:c.5405T>C NP_001394510.1:p.Leu1802Pro missense NM_001407582.1:c.5405T>C NP_001394511.1:p.Leu1802Pro missense NM_001407583.1:c.5402T>C NP_001394512.1:p.Leu1801Pro missense NM_001407585.1:c.5402T>C NP_001394514.1:p.Leu1801Pro missense NM_001407587.1:c.5402T>C NP_001394516.1:p.Leu1801Pro missense NM_001407590.1:c.5399T>C NP_001394519.1:p.Leu1800Pro missense NM_001407591.1:c.5399T>C NP_001394520.1:p.Leu1800Pro missense NM_001407593.1:c.5339T>C NP_001394522.1:p.Leu1780Pro missense NM_001407594.1:c.5339T>C NP_001394523.1:p.Leu1780Pro missense NM_001407596.1:c.5339T>C NP_001394525.1:p.Leu1780Pro missense NM_001407597.1:c.5339T>C NP_001394526.1:p.Leu1780Pro missense NM_001407598.1:c.5339T>C NP_001394527.1:p.Leu1780Pro missense NM_001407602.1:c.5339T>C NP_001394531.1:p.Leu1780Pro missense NM_001407603.1:c.5339T>C NP_001394532.1:p.Leu1780Pro missense NM_001407605.1:c.5339T>C NP_001394534.1:p.Leu1780Pro missense NM_001407610.1:c.5336T>C NP_001394539.1:p.Leu1779Pro missense NM_001407611.1:c.5336T>C NP_001394540.1:p.Leu1779Pro missense NM_001407612.1:c.5336T>C NP_001394541.1:p.Leu1779Pro missense NM_001407613.1:c.5336T>C NP_001394542.1:p.Leu1779Pro missense NM_001407614.1:c.5336T>C NP_001394543.1:p.Leu1779Pro missense NM_001407615.1:c.5336T>C NP_001394544.1:p.Leu1779Pro missense NM_001407616.1:c.5336T>C NP_001394545.1:p.Leu1779Pro missense NM_001407617.1:c.5336T>C NP_001394546.1:p.Leu1779Pro missense NM_001407618.1:c.5336T>C NP_001394547.1:p.Leu1779Pro missense NM_001407619.1:c.5336T>C NP_001394548.1:p.Leu1779Pro missense NM_001407620.1:c.5336T>C NP_001394549.1:p.Leu1779Pro missense NM_001407621.1:c.5336T>C NP_001394550.1:p.Leu1779Pro missense NM_001407622.1:c.5336T>C NP_001394551.1:p.Leu1779Pro missense NM_001407623.1:c.5336T>C NP_001394552.1:p.Leu1779Pro missense NM_001407624.1:c.5336T>C NP_001394553.1:p.Leu1779Pro missense NM_001407625.1:c.5336T>C NP_001394554.1:p.Leu1779Pro missense NM_001407626.1:c.5336T>C NP_001394555.1:p.Leu1779Pro missense NM_001407627.1:c.5333T>C NP_001394556.1:p.Leu1778Pro missense NM_001407628.1:c.5333T>C NP_001394557.1:p.Leu1778Pro missense NM_001407629.1:c.5333T>C NP_001394558.1:p.Leu1778Pro missense NM_001407630.1:c.5333T>C NP_001394559.1:p.Leu1778Pro missense NM_001407631.1:c.5333T>C NP_001394560.1:p.Leu1778Pro missense NM_001407632.1:c.5333T>C NP_001394561.1:p.Leu1778Pro missense NM_001407633.1:c.5333T>C NP_001394562.1:p.Leu1778Pro missense NM_001407634.1:c.5333T>C NP_001394563.1:p.Leu1778Pro missense NM_001407635.1:c.5333T>C NP_001394564.1:p.Leu1778Pro missense NM_001407636.1:c.5333T>C NP_001394565.1:p.Leu1778Pro missense NM_001407637.1:c.5333T>C NP_001394566.1:p.Leu1778Pro missense NM_001407638.1:c.5333T>C NP_001394567.1:p.Leu1778Pro missense NM_001407639.1:c.5333T>C NP_001394568.1:p.Leu1778Pro missense NM_001407640.1:c.5333T>C NP_001394569.1:p.Leu1778Pro missense NM_001407641.1:c.5333T>C NP_001394570.1:p.Leu1778Pro missense NM_001407642.1:c.5333T>C NP_001394571.1:p.Leu1778Pro missense NM_001407644.1:c.5330T>C NP_001394573.1:p.Leu1777Pro missense NM_001407645.1:c.5330T>C NP_001394574.1:p.Leu1777Pro missense NM_001407646.1:c.5327T>C NP_001394575.1:p.Leu1776Pro missense NM_001407647.1:c.5324T>C NP_001394576.1:p.Leu1775Pro missense NM_001407648.1:c.5282T>C NP_001394577.1:p.Leu1761Pro missense NM_001407649.1:c.5279T>C NP_001394578.1:p.Leu1760Pro missense NM_001407652.1:c.5261T>C NP_001394581.1:p.Leu1754Pro missense NM_001407653.1:c.5261T>C NP_001394582.1:p.Leu1754Pro missense NM_001407654.1:c.5261T>C NP_001394583.1:p.Leu1754Pro missense NM_001407655.1:c.5261T>C NP_001394584.1:p.Leu1754Pro missense NM_001407656.1:c.5258T>C NP_001394585.1:p.Leu1753Pro missense NM_001407657.1:c.5258T>C NP_001394586.1:p.Leu1753Pro missense NM_001407658.1:c.5258T>C NP_001394587.1:p.Leu1753Pro missense NM_001407659.1:c.5255T>C NP_001394588.1:p.Leu1752Pro missense NM_001407660.1:c.5255T>C NP_001394589.1:p.Leu1752Pro missense NM_001407661.1:c.5255T>C NP_001394590.1:p.Leu1752Pro missense NM_001407662.1:c.5255T>C NP_001394591.1:p.Leu1752Pro missense NM_001407663.1:c.5255T>C NP_001394592.1:p.Leu1752Pro missense NM_001407664.1:c.5216T>C NP_001394593.1:p.Leu1739Pro missense NM_001407665.1:c.5216T>C NP_001394594.1:p.Leu1739Pro missense NM_001407666.1:c.5216T>C NP_001394595.1:p.Leu1739Pro missense NM_001407667.1:c.5216T>C NP_001394596.1:p.Leu1739Pro missense NM_001407668.1:c.5216T>C NP_001394597.1:p.Leu1739Pro missense NM_001407669.1:c.5216T>C NP_001394598.1:p.Leu1739Pro missense NM_001407670.1:c.5213T>C NP_001394599.1:p.Leu1738Pro missense NM_001407671.1:c.5213T>C NP_001394600.1:p.Leu1738Pro missense NM_001407672.1:c.5213T>C NP_001394601.1:p.Leu1738Pro missense NM_001407673.1:c.5213T>C NP_001394602.1:p.Leu1738Pro missense NM_001407674.1:c.5213T>C NP_001394603.1:p.Leu1738Pro missense NM_001407675.1:c.5213T>C NP_001394604.1:p.Leu1738Pro missense NM_001407676.1:c.5213T>C NP_001394605.1:p.Leu1738Pro missense NM_001407677.1:c.5213T>C NP_001394606.1:p.Leu1738Pro missense NM_001407678.1:c.5213T>C NP_001394607.1:p.Leu1738Pro missense NM_001407679.1:c.5213T>C NP_001394608.1:p.Leu1738Pro missense NM_001407680.1:c.5213T>C NP_001394609.1:p.Leu1738Pro missense NM_001407681.1:c.5210T>C NP_001394610.1:p.Leu1737Pro missense NM_001407682.1:c.5210T>C NP_001394611.1:p.Leu1737Pro missense NM_001407683.1:c.5210T>C NP_001394612.1:p.Leu1737Pro missense NM_001407685.1:c.5210T>C NP_001394614.1:p.Leu1737Pro missense NM_001407686.1:c.5210T>C NP_001394615.1:p.Leu1737Pro missense NM_001407687.1:c.5210T>C NP_001394616.1:p.Leu1737Pro missense NM_001407688.1:c.5210T>C NP_001394617.1:p.Leu1737Pro missense NM_001407689.1:c.5210T>C NP_001394618.1:p.Leu1737Pro missense NM_001407690.1:c.5207T>C NP_001394619.1:p.Leu1736Pro missense NM_001407691.1:c.5207T>C NP_001394620.1:p.Leu1736Pro missense NM_001407692.1:c.5198T>C NP_001394621.1:p.Leu1733Pro missense NM_001407694.1:c.5198T>C NP_001394623.1:p.Leu1733Pro missense NM_001407695.1:c.5198T>C NP_001394624.1:p.Leu1733Pro missense NM_001407696.1:c.5198T>C NP_001394625.1:p.Leu1733Pro missense NM_001407697.1:c.5198T>C NP_001394626.1:p.Leu1733Pro missense NM_001407698.1:c.5198T>C NP_001394627.1:p.Leu1733Pro missense NM_001407724.1:c.5198T>C NP_001394653.1:p.Leu1733Pro missense NM_001407725.1:c.5198T>C NP_001394654.1:p.Leu1733Pro missense NM_001407726.1:c.5198T>C NP_001394655.1:p.Leu1733Pro missense NM_001407727.1:c.5198T>C NP_001394656.1:p.Leu1733Pro missense NM_001407728.1:c.5198T>C NP_001394657.1:p.Leu1733Pro missense NM_001407729.1:c.5198T>C NP_001394658.1:p.Leu1733Pro missense NM_001407730.1:c.5198T>C NP_001394659.1:p.Leu1733Pro missense NM_001407731.1:c.5198T>C NP_001394660.1:p.Leu1733Pro missense NM_001407732.1:c.5195T>C NP_001394661.1:p.Leu1732Pro missense NM_001407733.1:c.5195T>C NP_001394662.1:p.Leu1732Pro missense NM_001407734.1:c.5195T>C NP_001394663.1:p.Leu1732Pro missense NM_001407735.1:c.5195T>C NP_001394664.1:p.Leu1732Pro missense NM_001407736.1:c.5195T>C NP_001394665.1:p.Leu1732Pro missense NM_001407737.1:c.5195T>C NP_001394666.1:p.Leu1732Pro missense NM_001407738.1:c.5195T>C NP_001394667.1:p.Leu1732Pro missense NM_001407739.1:c.5195T>C NP_001394668.1:p.Leu1732Pro missense NM_001407740.1:c.5195T>C NP_001394669.1:p.Leu1732Pro missense NM_001407741.1:c.5195T>C NP_001394670.1:p.Leu1732Pro missense NM_001407742.1:c.5195T>C NP_001394671.1:p.Leu1732Pro missense NM_001407743.1:c.5195T>C NP_001394672.1:p.Leu1732Pro missense NM_001407744.1:c.5195T>C NP_001394673.1:p.Leu1732Pro missense NM_001407745.1:c.5195T>C NP_001394674.1:p.Leu1732Pro missense NM_001407746.1:c.5195T>C NP_001394675.1:p.Leu1732Pro missense NM_001407747.1:c.5195T>C NP_001394676.1:p.Leu1732Pro missense NM_001407748.1:c.5195T>C NP_001394677.1:p.Leu1732Pro missense NM_001407749.1:c.5195T>C NP_001394678.1:p.Leu1732Pro missense NM_001407750.1:c.5195T>C NP_001394679.1:p.Leu1732Pro missense NM_001407751.1:c.5195T>C NP_001394680.1:p.Leu1732Pro missense NM_001407752.1:c.5195T>C NP_001394681.1:p.Leu1732Pro missense NM_001407838.1:c.5192T>C NP_001394767.1:p.Leu1731Pro missense NM_001407839.1:c.5192T>C NP_001394768.1:p.Leu1731Pro missense NM_001407841.1:c.5192T>C NP_001394770.1:p.Leu1731Pro missense NM_001407842.1:c.5192T>C NP_001394771.1:p.Leu1731Pro missense NM_001407843.1:c.5192T>C NP_001394772.1:p.Leu1731Pro missense NM_001407844.1:c.5192T>C NP_001394773.1:p.Leu1731Pro missense NM_001407845.1:c.5192T>C NP_001394774.1:p.Leu1731Pro missense NM_001407846.1:c.5192T>C NP_001394775.1:p.Leu1731Pro missense NM_001407847.1:c.5192T>C NP_001394776.1:p.Leu1731Pro missense NM_001407848.1:c.5192T>C NP_001394777.1:p.Leu1731Pro missense NM_001407849.1:c.5192T>C NP_001394778.1:p.Leu1731Pro missense NM_001407850.1:c.5192T>C NP_001394779.1:p.Leu1731Pro missense NM_001407851.1:c.5192T>C NP_001394780.1:p.Leu1731Pro missense NM_001407852.1:c.5192T>C NP_001394781.1:p.Leu1731Pro missense NM_001407853.1:c.5192T>C NP_001394782.1:p.Leu1731Pro missense NM_001407862.1:c.5138T>C NP_001394791.1:p.Leu1713Pro missense NM_001407863.1:c.5135T>C NP_001394792.1:p.Leu1712Pro missense NM_001407874.1:c.5132T>C NP_001394803.1:p.Leu1711Pro missense NM_001407875.1:c.5132T>C NP_001394804.1:p.Leu1711Pro missense NM_001407879.1:c.5129T>C NP_001394808.1:p.Leu1710Pro missense NM_001407881.1:c.5129T>C NP_001394810.1:p.Leu1710Pro missense NM_001407882.1:c.5129T>C NP_001394811.1:p.Leu1710Pro missense NM_001407884.1:c.5129T>C NP_001394813.1:p.Leu1710Pro missense NM_001407885.1:c.5129T>C NP_001394814.1:p.Leu1710Pro missense NM_001407886.1:c.5129T>C NP_001394815.1:p.Leu1710Pro missense NM_001407887.1:c.5129T>C NP_001394816.1:p.Leu1710Pro missense NM_001407889.1:c.5129T>C NP_001394818.1:p.Leu1710Pro missense NM_001407894.1:c.5126T>C NP_001394823.1:p.Leu1709Pro missense NM_001407895.1:c.5126T>C NP_001394824.1:p.Leu1709Pro missense NM_001407896.1:c.5126T>C NP_001394825.1:p.Leu1709Pro missense NM_001407897.1:c.5126T>C NP_001394826.1:p.Leu1709Pro missense NM_001407898.1:c.5126T>C NP_001394827.1:p.Leu1709Pro missense NM_001407899.1:c.5126T>C NP_001394828.1:p.Leu1709Pro missense NM_001407900.1:c.5126T>C NP_001394829.1:p.Leu1709Pro missense NM_001407902.1:c.5126T>C NP_001394831.1:p.Leu1709Pro missense NM_001407904.1:c.5126T>C NP_001394833.1:p.Leu1709Pro missense NM_001407906.1:c.5126T>C NP_001394835.1:p.Leu1709Pro missense NM_001407907.1:c.5126T>C NP_001394836.1:p.Leu1709Pro missense NM_001407908.1:c.5126T>C NP_001394837.1:p.Leu1709Pro missense NM_001407909.1:c.5126T>C NP_001394838.1:p.Leu1709Pro missense NM_001407910.1:c.5126T>C NP_001394839.1:p.Leu1709Pro missense NM_001407915.1:c.5123T>C NP_001394844.1:p.Leu1708Pro missense NM_001407916.1:c.5123T>C NP_001394845.1:p.Leu1708Pro missense NM_001407917.1:c.5123T>C NP_001394846.1:p.Leu1708Pro missense NM_001407918.1:c.5123T>C NP_001394847.1:p.Leu1708Pro missense NM_001407920.1:c.5075T>C NP_001394849.1:p.Leu1692Pro missense NM_001407921.1:c.5075T>C NP_001394850.1:p.Leu1692Pro missense NM_001407922.1:c.5075T>C NP_001394851.1:p.Leu1692Pro missense NM_001407923.1:c.5075T>C NP_001394852.1:p.Leu1692Pro missense NM_001407924.1:c.5075T>C NP_001394853.1:p.Leu1692Pro missense NM_001407925.1:c.5075T>C NP_001394854.1:p.Leu1692Pro missense NM_001407926.1:c.5075T>C NP_001394855.1:p.Leu1692Pro missense NM_001407927.1:c.5072T>C NP_001394856.1:p.Leu1691Pro missense NM_001407928.1:c.5072T>C NP_001394857.1:p.Leu1691Pro missense NM_001407929.1:c.5072T>C NP_001394858.1:p.Leu1691Pro missense NM_001407930.1:c.5072T>C NP_001394859.1:p.Leu1691Pro missense NM_001407931.1:c.5072T>C NP_001394860.1:p.Leu1691Pro missense NM_001407932.1:c.5072T>C NP_001394861.1:p.Leu1691Pro missense NM_001407933.1:c.5072T>C NP_001394862.1:p.Leu1691Pro missense NM_001407934.1:c.5069T>C NP_001394863.1:p.Leu1690Pro missense NM_001407935.1:c.5069T>C NP_001394864.1:p.Leu1690Pro missense NM_001407936.1:c.5069T>C NP_001394865.1:p.Leu1690Pro missense NM_001407946.1:c.5006T>C NP_001394875.1:p.Leu1669Pro missense NM_001407947.1:c.5006T>C NP_001394876.1:p.Leu1669Pro missense NM_001407948.1:c.5006T>C NP_001394877.1:p.Leu1669Pro missense NM_001407949.1:c.5006T>C NP_001394878.1:p.Leu1669Pro missense NM_001407950.1:c.5003T>C NP_001394879.1:p.Leu1668Pro missense NM_001407951.1:c.5003T>C NP_001394880.1:p.Leu1668Pro missense NM_001407952.1:c.5003T>C NP_001394881.1:p.Leu1668Pro missense NM_001407953.1:c.5003T>C NP_001394882.1:p.Leu1668Pro missense NM_001407954.1:c.5003T>C NP_001394883.1:p.Leu1668Pro missense NM_001407955.1:c.5003T>C NP_001394884.1:p.Leu1668Pro missense NM_001407956.1:c.5000T>C NP_001394885.1:p.Leu1667Pro missense NM_001407957.1:c.5000T>C NP_001394886.1:p.Leu1667Pro missense NM_001407958.1:c.5000T>C NP_001394887.1:p.Leu1667Pro missense NM_001407959.1:c.4958T>C NP_001394888.1:p.Leu1653Pro missense NM_001407960.1:c.4955T>C NP_001394889.1:p.Leu1652Pro missense NM_001407962.1:c.4955T>C NP_001394891.1:p.Leu1652Pro missense NM_001407963.1:c.4952T>C NP_001394892.1:p.Leu1651Pro missense NM_001407964.1:c.4877T>C NP_001394893.1:p.Leu1626Pro missense NM_001407965.1:c.4832T>C NP_001394894.1:p.Leu1611Pro missense NM_001407966.1:c.4451T>C NP_001394895.1:p.Leu1484Pro missense NM_001407967.1:c.4448T>C NP_001394896.1:p.Leu1483Pro missense NM_001407968.1:c.2735T>C NP_001394897.1:p.Leu912Pro missense NM_001407969.1:c.2732T>C NP_001394898.1:p.Leu911Pro missense NM_001407970.1:c.2096T>C NP_001394899.1:p.Leu699Pro missense NM_001407971.1:c.2096T>C NP_001394900.1:p.Leu699Pro missense NM_001407972.1:c.2093T>C NP_001394901.1:p.Leu698Pro missense NM_001407973.1:c.2030T>C NP_001394902.1:p.Leu677Pro missense NM_001407974.1:c.2030T>C NP_001394903.1:p.Leu677Pro missense NM_001407975.1:c.2030T>C NP_001394904.1:p.Leu677Pro missense NM_001407976.1:c.2030T>C NP_001394905.1:p.Leu677Pro missense NM_001407977.1:c.2030T>C NP_001394906.1:p.Leu677Pro missense NM_001407978.1:c.2030T>C NP_001394907.1:p.Leu677Pro missense NM_001407979.1:c.2027T>C NP_001394908.1:p.Leu676Pro missense NM_001407980.1:c.2027T>C NP_001394909.1:p.Leu676Pro missense NM_001407981.1:c.2027T>C NP_001394910.1:p.Leu676Pro missense NM_001407982.1:c.2027T>C NP_001394911.1:p.Leu676Pro missense NM_001407983.1:c.2027T>C NP_001394912.1:p.Leu676Pro missense NM_001407984.1:c.2027T>C NP_001394913.1:p.Leu676Pro missense NM_001407985.1:c.2027T>C NP_001394914.1:p.Leu676Pro missense NM_001407986.1:c.2027T>C NP_001394915.1:p.Leu676Pro missense NM_001407990.1:c.2027T>C NP_001394919.1:p.Leu676Pro missense NM_001407991.1:c.2027T>C NP_001394920.1:p.Leu676Pro missense NM_001407992.1:c.2027T>C NP_001394921.1:p.Leu676Pro missense NM_001407993.1:c.2027T>C NP_001394922.1:p.Leu676Pro missense NM_001408392.1:c.2024T>C NP_001395321.1:p.Leu675Pro missense NM_001408396.1:c.2024T>C NP_001395325.1:p.Leu675Pro missense NM_001408397.1:c.2024T>C NP_001395326.1:p.Leu675Pro missense NM_001408398.1:c.2024T>C NP_001395327.1:p.Leu675Pro missense NM_001408399.1:c.2024T>C NP_001395328.1:p.Leu675Pro missense NM_001408400.1:c.2024T>C NP_001395329.1:p.Leu675Pro missense NM_001408401.1:c.2024T>C NP_001395330.1:p.Leu675Pro missense NM_001408402.1:c.2024T>C NP_001395331.1:p.Leu675Pro missense NM_001408403.1:c.2024T>C NP_001395332.1:p.Leu675Pro missense NM_001408404.1:c.2024T>C NP_001395333.1:p.Leu675Pro missense NM_001408406.1:c.2021T>C NP_001395335.1:p.Leu674Pro missense NM_001408407.1:c.2021T>C NP_001395336.1:p.Leu674Pro missense NM_001408408.1:c.2021T>C NP_001395337.1:p.Leu674Pro missense NM_001408409.1:c.2018T>C NP_001395338.1:p.Leu673Pro missense NM_001408410.1:c.1955T>C NP_001395339.1:p.Leu652Pro missense NM_001408411.1:c.1952T>C NP_001395340.1:p.Leu651Pro missense NM_001408412.1:c.1949T>C NP_001395341.1:p.Leu650Pro missense NM_001408413.1:c.1949T>C NP_001395342.1:p.Leu650Pro missense NM_001408414.1:c.1949T>C NP_001395343.1:p.Leu650Pro missense NM_001408415.1:c.1949T>C NP_001395344.1:p.Leu650Pro missense NM_001408416.1:c.1949T>C NP_001395345.1:p.Leu650Pro missense NM_001408418.1:c.1913T>C NP_001395347.1:p.Leu638Pro missense NM_001408419.1:c.1913T>C NP_001395348.1:p.Leu638Pro missense NM_001408420.1:c.1913T>C NP_001395349.1:p.Leu638Pro missense NM_001408421.1:c.1910T>C NP_001395350.1:p.Leu637Pro missense NM_001408422.1:c.1910T>C NP_001395351.1:p.Leu637Pro missense NM_001408423.1:c.1910T>C NP_001395352.1:p.Leu637Pro missense NM_001408424.1:c.1910T>C NP_001395353.1:p.Leu637Pro missense NM_001408425.1:c.1907T>C NP_001395354.1:p.Leu636Pro missense NM_001408426.1:c.1907T>C NP_001395355.1:p.Leu636Pro missense NM_001408427.1:c.1907T>C NP_001395356.1:p.Leu636Pro missense NM_001408428.1:c.1907T>C NP_001395357.1:p.Leu636Pro missense NM_001408429.1:c.1907T>C NP_001395358.1:p.Leu636Pro missense NM_001408430.1:c.1907T>C NP_001395359.1:p.Leu636Pro missense NM_001408431.1:c.1907T>C NP_001395360.1:p.Leu636Pro missense NM_001408432.1:c.1904T>C NP_001395361.1:p.Leu635Pro missense NM_001408433.1:c.1904T>C NP_001395362.1:p.Leu635Pro missense NM_001408434.1:c.1904T>C NP_001395363.1:p.Leu635Pro missense NM_001408435.1:c.1904T>C NP_001395364.1:p.Leu635Pro missense NM_001408436.1:c.1904T>C NP_001395365.1:p.Leu635Pro missense NM_001408437.1:c.1904T>C NP_001395366.1:p.Leu635Pro missense NM_001408438.1:c.1904T>C NP_001395367.1:p.Leu635Pro missense NM_001408439.1:c.1904T>C NP_001395368.1:p.Leu635Pro missense NM_001408440.1:c.1904T>C NP_001395369.1:p.Leu635Pro missense NM_001408441.1:c.1904T>C NP_001395370.1:p.Leu635Pro missense NM_001408442.1:c.1904T>C NP_001395371.1:p.Leu635Pro missense NM_001408443.1:c.1904T>C NP_001395372.1:p.Leu635Pro missense NM_001408444.1:c.1904T>C NP_001395373.1:p.Leu635Pro missense NM_001408445.1:c.1901T>C NP_001395374.1:p.Leu634Pro missense NM_001408446.1:c.1901T>C NP_001395375.1:p.Leu634Pro missense NM_001408447.1:c.1901T>C NP_001395376.1:p.Leu634Pro missense NM_001408448.1:c.1901T>C NP_001395377.1:p.Leu634Pro missense NM_001408450.1:c.1901T>C NP_001395379.1:p.Leu634Pro missense NM_001408451.1:c.1895T>C NP_001395380.1:p.Leu632Pro missense NM_001408452.1:c.1889T>C NP_001395381.1:p.Leu630Pro missense NM_001408453.1:c.1889T>C NP_001395382.1:p.Leu630Pro missense NM_001408454.1:c.1889T>C NP_001395383.1:p.Leu630Pro missense NM_001408455.1:c.1889T>C NP_001395384.1:p.Leu630Pro missense NM_001408456.1:c.1889T>C NP_001395385.1:p.Leu630Pro missense NM_001408457.1:c.1889T>C NP_001395386.1:p.Leu630Pro missense NM_001408458.1:c.1886T>C NP_001395387.1:p.Leu629Pro missense NM_001408459.1:c.1886T>C NP_001395388.1:p.Leu629Pro missense NM_001408460.1:c.1886T>C NP_001395389.1:p.Leu629Pro missense NM_001408461.1:c.1886T>C NP_001395390.1:p.Leu629Pro missense NM_001408462.1:c.1886T>C NP_001395391.1:p.Leu629Pro missense NM_001408463.1:c.1886T>C NP_001395392.1:p.Leu629Pro missense NM_001408464.1:c.1886T>C NP_001395393.1:p.Leu629Pro missense NM_001408465.1:c.1886T>C NP_001395394.1:p.Leu629Pro missense NM_001408466.1:c.1886T>C NP_001395395.1:p.Leu629Pro missense NM_001408467.1:c.1886T>C NP_001395396.1:p.Leu629Pro missense NM_001408468.1:c.1883T>C NP_001395397.1:p.Leu628Pro missense NM_001408469.1:c.1883T>C NP_001395398.1:p.Leu628Pro missense NM_001408470.1:c.1883T>C NP_001395399.1:p.Leu628Pro missense NM_001408474.1:c.1829T>C NP_001395403.1:p.Leu610Pro missense NM_001408475.1:c.1826T>C NP_001395404.1:p.Leu609Pro missense NM_001408476.1:c.1826T>C NP_001395405.1:p.Leu609Pro missense NM_001408478.1:c.1820T>C NP_001395407.1:p.Leu607Pro missense NM_001408479.1:c.1820T>C NP_001395408.1:p.Leu607Pro missense NM_001408480.1:c.1820T>C NP_001395409.1:p.Leu607Pro missense NM_001408481.1:c.1817T>C NP_001395410.1:p.Leu606Pro missense NM_001408482.1:c.1817T>C NP_001395411.1:p.Leu606Pro missense NM_001408483.1:c.1817T>C NP_001395412.1:p.Leu606Pro missense NM_001408484.1:c.1817T>C NP_001395413.1:p.Leu606Pro missense NM_001408485.1:c.1817T>C NP_001395414.1:p.Leu606Pro missense NM_001408489.1:c.1817T>C NP_001395418.1:p.Leu606Pro missense NM_001408490.1:c.1817T>C NP_001395419.1:p.Leu606Pro missense NM_001408491.1:c.1817T>C NP_001395420.1:p.Leu606Pro missense NM_001408492.1:c.1814T>C NP_001395421.1:p.Leu605Pro missense NM_001408493.1:c.1814T>C NP_001395422.1:p.Leu605Pro missense NM_001408494.1:c.1790T>C NP_001395423.1:p.Leu597Pro missense NM_001408495.1:c.1784T>C NP_001395424.1:p.Leu595Pro missense NM_001408496.1:c.1766T>C NP_001395425.1:p.Leu589Pro missense NM_001408497.1:c.1766T>C NP_001395426.1:p.Leu589Pro missense NM_001408498.1:c.1766T>C NP_001395427.1:p.Leu589Pro missense NM_001408499.1:c.1766T>C NP_001395428.1:p.Leu589Pro missense NM_001408500.1:c.1766T>C NP_001395429.1:p.Leu589Pro missense NM_001408501.1:c.1766T>C NP_001395430.1:p.Leu589Pro missense NM_001408502.1:c.1763T>C NP_001395431.1:p.Leu588Pro missense NM_001408503.1:c.1763T>C NP_001395432.1:p.Leu588Pro missense NM_001408504.1:c.1763T>C NP_001395433.1:p.Leu588Pro missense NM_001408505.1:c.1760T>C NP_001395434.1:p.Leu587Pro missense NM_001408506.1:c.1703T>C NP_001395435.1:p.Leu568Pro missense NM_001408507.1:c.1700T>C NP_001395436.1:p.Leu567Pro missense NM_001408508.1:c.1691T>C NP_001395437.1:p.Leu564Pro missense NM_001408509.1:c.1688T>C NP_001395438.1:p.Leu563Pro missense NM_001408510.1:c.1649T>C NP_001395439.1:p.Leu550Pro missense NM_001408511.1:c.1646T>C NP_001395440.1:p.Leu549Pro missense NM_001408512.1:c.1526T>C NP_001395441.1:p.Leu509Pro missense NM_001408513.1:c.1499T>C NP_001395442.1:p.Leu500Pro missense NM_001408514.1:c.1103T>C NP_001395443.1:p.Leu368Pro missense NM_007297.4:c.5198T>C NP_009228.2:p.Leu1733Pro missense NM_007298.4:c.2027T>C NP_009229.2:p.Leu676Pro missense NM_007299.4:c.2021-1485T>C intron variant NM_007300.4:c.5402T>C NP_009231.2:p.Leu1801Pro missense NM_007304.2:c.2027T>C NP_009235.2:p.Leu676Pro missense NR_027676.2:n.5516T>C non-coding transcript variant NC_000017.11:g.43049188A>G NC_000017.10:g.41201205A>G NG_005905.2:g.168796T>C LRG_292:g.168796T>C LRG_292t1:c.5339T>C LRG_292p1:p.Leu1780Pro U14680.1:n.5458T>C - Protein change
- L1780P, L676P, L1733P, L1801P, L1484P, L1653P, L1667P, L1668P, L1692P, L1711P, L1712P, L1713P, L1731P, L1732P, L500P, L509P, L589P, L605P, L606P, L607P, L609P, L628P, L634P, L650P, L698P, L699P, L911P, L1483P, L1611P, L1669P, L1691P, L1708P, L1738P, L1739P, L1761P, L1775P, L1779P, L1800P, L368P, L550P, L588P, L595P, L636P, L652P, L674P, L677P, L1709P, L1736P, L1752P, L1753P, L1754P, L1777P, L1778P, L564P, L567P, L587P, L610P, L637P, L638P, L651P, L675P, L912P, L1626P, L1651P, L1652P, L1690P, L1710P, L1737P, L1760P, L1776P, L1802P, L549P, L563P, L568P, L597P, L629P, L630P, L632P, L635P, L673P
- Other names
- -
- Canonical SPDI
- NC_000017.11:43049187:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
variation affecting protein function; Variation Ontology [ VariO:0003]functionally_abnormal; Sequence Ontology [ SO:0002218]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5339T>C, a MISSENSE variant, produced a function score of -2.35, 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.
-
The Genome Aggregation Database (gnomAD), exomes 0.00001
- Links
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 |
13050 | 14856 | |
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 (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 2, 2024 | RCV000048948.14 | |
| Pathogenic (5) |
criteria provided, single submitter
|
Jun 15, 2016 | RCV000112624.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 12, 2023 | RCV000132201.8 | |
| Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 2, 2023 | RCV000236823.5 |
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
(Jan 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004803448.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant summary: BRCA1 c.5339T>C (p.Leu1780Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: BRCA1 c.5339T>C (p.Leu1780Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251430 control chromosomes. c.5339T>C has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. These data indicate that the variant is very likely to be associated with disease. At least one functional study reports experimental evidence evaluating an impact on protein function and showed damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Dec 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000187283.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.L1780P variant (also known as c.5339T>C), located in coding exon 20 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.L1780P variant (also known as c.5339T>C), located in coding exon 20 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5339. The leucine at codon 1780 is replaced by proline, an amino acid with similar properties. This alteration has been detected in many Korean case reports and case-control studies of breast and/or ovarian cancer and is statistically significantly over-represented in the affected populations versus control populations (Choi DH et al. J. Clin. Oncol. 2004 May;22:1638-45; Han SH et al. Clin. Genet. 2006 Dec;70:496-501; Jang JH et al. J. Hum. Genet. 2012 Mar;57:212-5; Yoon KA et al. Cancer Res Treat. 2017 Jul;49:627-634; Eoh KJ et al. Cancer Res Treat. 2018 Jul;50:917-925; Park JS et al. Cancer Res Treat. 2017 Oct;49:1012-1021; Ryu JM et al. Breast. 2017 Jun;33:109-116; Choi MC et al. J Gynecol Oncol. 2018 Jul;29:e43). This variant segregated with disease in two of these studies and is also suggested to be a Korean founder mutation (Ryu JM et al. Breast. 2017 Jun;33:109-116; Park JS et al. Cancer Res Treat. 2017 Oct;49:1012-1021). Analysis of this alteration in yeast, bacterial and mammalian systems show that it is functionally deleterious in terms of cell survival, transcriptional activation, protein binding and protein folding (Findlay GM et al. Nature. 2018 10;562:217-222; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Rowling PJ et al. J. Biol. Chem. 2010 Jun;285:20080-7; Hayes F et al. Cancer Res. 2000 May;60:2411-8). Of note, this alteration is also designated as 5458T>C in some published literature. This amino acid position is highly conserved on sequence alignment. 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)
|
|
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Pathogenic
(Jul 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Center for Breast Cancer, National Cancer Center
Accession: SCV000484656.1
First in ClinVar: Jul 01, 2016 Last updated: Jul 01, 2016 |
Comment:
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. The c.5339T>C variant in the BRCA1 gene … (more)
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. The c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. It was not detected in 421 healthy controls. We were able to recruit family members of the proband harboring the c.5339T>C variant in the BRCA1 gene. As shown in the pedigree in the published article, two breast cancer patients in this family and the proband were also diagnosed with ovarian cancer 2 years after being diagnosed with breast cancer. The father of the proband also carried the same UV, and his sister died of breast cancer at the age of 46. Another patient who harbored the same variant was diagnosed with breast cancer at the age of 33. Her mother suffered from ovarian cancer and could not participate in this study. The c.5339T>C variant results in an amino acid change from leucine to proline at position 1780. The predicted structure shows that the mutation site is in the middle of a helix in the BRCT domain of BRCA1, forming a hydrophobic patch with its surrounding residues. The BRCT domain is known to recognize and bind phosphorylated pSXXF motifs of FAM175A/Abraxas to recruit BRCA1 to regions of DNA damage. (less)
Number of individuals with the variant: 4
Clinical Features:
Breast carcinoma (present)
Sex: female
Ethnicity/Population group: Asian
Geographic origin: Korea
|
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Pathogenic
(Jun 15, 2016)
|
criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Cancer Prevention Center, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine
Accession: SCV000512304.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Comment:
We observed that 11 HBOC patients with L1780P variant showed typical clinicopathological feature of patients with BRCA1 mutations. When we apply the ACMG standards and … (more)
We observed that 11 HBOC patients with L1780P variant showed typical clinicopathological feature of patients with BRCA1 mutations. When we apply the ACMG standards and guideline for reclassification of L1780P, L1780P is a highly suspected of pathogenic varints of BRCA1. A previous study (Lee et al, 2010) also indicated that L1780P mutation causes adverse effects on cells in functional anlayses. Our re-classification according to the ACMG guidelines for L1780P variant published in Cancer Research and Treatment (Park et al, 2017, e-pub). (less)
Number of individuals with the variant: 11
Clinical Features:
Breast carcinoma (present)
Age: 34-53 years
Sex: mixed
Ethnicity/Population group: Asian
Geographic origin: Korea
|
|
|
Pathogenic
(May 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Breast Center, Key Laboratory of Carcinogenesis and Translational Research
Accession: SCV001430320.1
First in ClinVar: Aug 22, 2020 Last updated: Aug 22, 2020 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: Chinese
|
|
|
Likely pathogenic
(Jun 30, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000293458.12
First in ClinVar: Jul 24, 2016 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect: absent or reduced protease sensitivity, binding activity and specificity, cell survival, and transcription activity (Hayes 2000, Lee 2010, … (more)
Published functional studies demonstrate a damaging effect: absent or reduced protease sensitivity, binding activity and specificity, cell survival, and transcription activity (Hayes 2000, Lee 2010, Findlay 2018); Observed in multiple individuals of Korean ancestry with breast and/or ovarian cancer (Choi 2004, Han 2006, Jang 2012, Eoh 2016, Yoon 2016, Ryu 2017); Case control studies in Korean women suggest this variant is associated with hereditary breast and ovarian cancer and may be a pathogenic Korean founder variant (Park 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 5458T>C; This variant is associated with the following publications: (PMID: 20378548, 19491284, 15235020, 27124784, 29240602, 27383479, 30415210, 20516115, 15117986, 17100994, 16949048, 22217648, 15172985, 10811118, 28111427, 28781887, 29020732, 28364669, 27658390, 28288110, 27488874, 29770616, 30209399, 30765603, 30309222, 32019279, 30350268) (less)
|
|
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Pathogenic
(Feb 02, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004219456.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.000008 (2/251430 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been … (more)
The frequency of this variant in the general population, 0.000008 (2/251430 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported as a founder mutation in the Korean population (PMIDs: 28111427 (2017), 28364669 (2017), 30309222 (2019)). It has been found in individuals with breast and/or ovarian cancer (PMIDs: 115117986 (2004), 17100994 (2006), 22217648 (2012), 27124784 (2016), 27488874 (2017), 27658390 (2017), 28364669 (2017), 28111427 (2017), 29020732 (2018), 29240602 (2018), 30309222 (2019), 30350268 (2019), 32019279 (2020), 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA1), and 34645131 (2022)). Additionally, the variant has been reported in healthy individuals (PMIDs: 17100994 (2006), 22217648 (2012), and 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA1)). Functional studies describe the variant as having a strong impact on the BRCA1 gene that results in the loss of protein function (PMIDs: 20516115 (2010), 30209399 (2018), 30415210 (2018), 30765603 (2019), 31907386 (2020), 32803532 (2020), 32546644 (2020), and 33087888 (2021)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Apr 08, 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: SCV000076961.10
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 10811118, 20378548, 20516115, … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 10811118, 20378548, 20516115, 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: 55541). This missense change has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 15117986, 17100994, 22217648, 27124784, 27383479, 27488874, 27658390, 28111427, 28288110, 28364669, 29020732, 29770616). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs80357474, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1780 of the BRCA1 protein (p.Leu1780Pro). (less)
|
|
|
Uncertain significance
(Jun 20, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145469.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Asian
|
|
|
Pathogenic
(May 24, 2021)
|
no assertion criteria provided
Method: case-control
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
de novo
|
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)
Accession: SCV005061299.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024
Comment:
Observed de novo in patient (mather and father not mutated, filiation comfirmed). Previously reported as Korean founder (PMID: 28111427)
|
Secondary finding: no
|
|
|
Likely pathogenic
(Mar 02, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV004243918.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
|
Brotman Baty Institute, University of Washington
Accession: SCV001242658.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.35494389501738
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Comment:
Comment:
The p.L1780P variant (also known as c.5339T>C), located in coding exon 20 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5339. The leucine at codon 1780 is replaced by proline, an amino acid with similar properties. This alteration has been detected in many Korean case reports and case-control studies of breast and/or ovarian cancer and is statistically significantly over-represented in the affected populations versus control populations (Choi DH et al. J. Clin. Oncol. 2004 May;22:1638-45; Han SH et al. Clin. Genet. 2006 Dec;70:496-501; Jang JH et al. J. Hum. Genet. 2012 Mar;57:212-5; Yoon KA et al. Cancer Res Treat. 2017 Jul;49:627-634; Eoh KJ et al. Cancer Res Treat. 2018 Jul;50:917-925; Park JS et al. Cancer Res Treat. 2017 Oct;49:1012-1021; Ryu JM et al. Breast. 2017 Jun;33:109-116; Choi MC et al. J Gynecol Oncol. 2018 Jul;29:e43). This variant segregated with disease in two of these studies and is also suggested to be a Korean founder mutation (Ryu JM et al. Breast. 2017 Jun;33:109-116; Park JS et al. Cancer Res Treat. 2017 Oct;49:1012-1021). Analysis of this alteration in yeast, bacterial and mammalian systems show that it is functionally deleterious in terms of cell survival, transcriptional activation, protein binding and protein folding (Findlay GM et al. Nature. 2018 10;562:217-222; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Rowling PJ et al. J. Biol. Chem. 2010 Jun;285:20080-7; Hayes F et al. Cancer Res. 2000 May;60:2411-8). Of note, this alteration is also designated as 5458T>C in some published literature. This amino acid position is highly conserved on sequence alignment. 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.
Comment:
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. The c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. It was not detected in 421 healthy controls. We were able to recruit family members of the proband harboring the c.5339T>C variant in the BRCA1 gene. As shown in the pedigree in the published article, two breast cancer patients in this family and the proband were also diagnosed with ovarian cancer 2 years after being diagnosed with breast cancer. The father of the proband also carried the same UV, and his sister died of breast cancer at the age of 46. Another patient who harbored the same variant was diagnosed with breast cancer at the age of 33. Her mother suffered from ovarian cancer and could not participate in this study. The c.5339T>C variant results in an amino acid change from leucine to proline at position 1780. The predicted structure shows that the mutation site is in the middle of a helix in the BRCT domain of BRCA1, forming a hydrophobic patch with its surrounding residues. The BRCT domain is known to recognize and bind phosphorylated pSXXF motifs of FAM175A/Abraxas to recruit BRCA1 to regions of DNA damage.
Comment:
We observed that 11 HBOC patients with L1780P variant showed typical clinicopathological feature of patients with BRCA1 mutations. When we apply the ACMG standards and guideline for reclassification of L1780P, L1780P is a highly suspected of pathogenic varints of BRCA1. A previous study (Lee et al, 2010) also indicated that L1780P mutation causes adverse effects on cells in functional anlayses. Our re-classification according to the ACMG guidelines for L1780P variant published in Cancer Research and Treatment (Park et al, 2017, e-pub).
Comment:
Published functional studies demonstrate a damaging effect: absent or reduced protease sensitivity, binding activity and specificity, cell survival, and transcription activity (Hayes 2000, Lee 2010, Findlay 2018); Observed in multiple individuals of Korean ancestry with breast and/or ovarian cancer (Choi 2004, Han 2006, Jang 2012, Eoh 2016, Yoon 2016, Ryu 2017); Case control studies in Korean women suggest this variant is associated with hereditary breast and ovarian cancer and may be a pathogenic Korean founder variant (Park 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 5458T>C; This variant is associated with the following publications: (PMID: 20378548, 19491284, 15235020, 27124784, 29240602, 27383479, 30415210, 20516115, 15117986, 17100994, 16949048, 22217648, 15172985, 10811118, 28111427, 28781887, 29020732, 28364669, 27658390, 28288110, 27488874, 29770616, 30209399, 30765603, 30309222, 32019279, 30350268)
Comment:
The frequency of this variant in the general population, 0.000008 (2/251430 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported as a founder mutation in the Korean population (PMIDs: 28111427 (2017), 28364669 (2017), 30309222 (2019)). It has been found in individuals with breast and/or ovarian cancer (PMIDs: 115117986 (2004), 17100994 (2006), 22217648 (2012), 27124784 (2016), 27488874 (2017), 27658390 (2017), 28364669 (2017), 28111427 (2017), 29020732 (2018), 29240602 (2018), 30309222 (2019), 30350268 (2019), 32019279 (2020), 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA1), and 34645131 (2022)). Additionally, the variant has been reported in healthy individuals (PMIDs: 17100994 (2006), 22217648 (2012), and 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA1)). Functional studies describe the variant as having a strong impact on the BRCA1 gene that results in the loss of protein function (PMIDs: 20516115 (2010), 30209399 (2018), 30415210 (2018), 30765603 (2019), 31907386 (2020), 32803532 (2020), 32546644 (2020), and 33087888 (2021)). Based on the available information, this variant is classified as pathogenic.
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 10811118, 20378548, 20516115, 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: 55541). This missense change has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 15117986, 17100994, 22217648, 27124784, 27383479, 27488874, 27658390, 28111427, 28288110, 28364669, 29020732, 29770616). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs80357474, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1780 of the BRCA1 protein (p.Leu1780Pro).
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
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variation affecting protein function
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Cancer Prevention Center, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine
Accession: SCV000512304.1
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functionally_abnormal
|
Method citation(s):
|
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Brotman Baty Institute, University of Washington
Accession: SCV001242658.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5339T>C, a MISSENSE variant, produced a function score of -2.35, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5339T>C, a MISSENSE variant, produced a function score of -2.35, 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)
|
Comment:
Variant summary: BRCA1 c.5339T>C (p.Leu1780Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251430 control chromosomes. c.5339T>C has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. These data indicate that the variant is very likely to be associated with disease. At least one functional study reports experimental evidence evaluating an impact on protein function and showed damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The p.L1780P variant (also known as c.5339T>C), located in coding exon 20 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5339. The leucine at codon 1780 is replaced by proline, an amino acid with similar properties. This alteration has been detected in many Korean case reports and case-control studies of breast and/or ovarian cancer and is statistically significantly over-represented in the affected populations versus control populations (Choi DH et al. J. Clin. Oncol. 2004 May;22:1638-45; Han SH et al. Clin. Genet. 2006 Dec;70:496-501; Jang JH et al. J. Hum. Genet. 2012 Mar;57:212-5; Yoon KA et al. Cancer Res Treat. 2017 Jul;49:627-634; Eoh KJ et al. Cancer Res Treat. 2018 Jul;50:917-925; Park JS et al. Cancer Res Treat. 2017 Oct;49:1012-1021; Ryu JM et al. Breast. 2017 Jun;33:109-116; Choi MC et al. J Gynecol Oncol. 2018 Jul;29:e43). This variant segregated with disease in two of these studies and is also suggested to be a Korean founder mutation (Ryu JM et al. Breast. 2017 Jun;33:109-116; Park JS et al. Cancer Res Treat. 2017 Oct;49:1012-1021). Analysis of this alteration in yeast, bacterial and mammalian systems show that it is functionally deleterious in terms of cell survival, transcriptional activation, protein binding and protein folding (Findlay GM et al. Nature. 2018 10;562:217-222; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Rowling PJ et al. J. Biol. Chem. 2010 Jun;285:20080-7; Hayes F et al. Cancer Res. 2000 May;60:2411-8). Of note, this alteration is also designated as 5458T>C in some published literature. This amino acid position is highly conserved on sequence alignment. 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.
Comment:
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. The c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. It was not detected in 421 healthy controls. We were able to recruit family members of the proband harboring the c.5339T>C variant in the BRCA1 gene. As shown in the pedigree in the published article, two breast cancer patients in this family and the proband were also diagnosed with ovarian cancer 2 years after being diagnosed with breast cancer. The father of the proband also carried the same UV, and his sister died of breast cancer at the age of 46. Another patient who harbored the same variant was diagnosed with breast cancer at the age of 33. Her mother suffered from ovarian cancer and could not participate in this study. The c.5339T>C variant results in an amino acid change from leucine to proline at position 1780. The predicted structure shows that the mutation site is in the middle of a helix in the BRCT domain of BRCA1, forming a hydrophobic patch with its surrounding residues. The BRCT domain is known to recognize and bind phosphorylated pSXXF motifs of FAM175A/Abraxas to recruit BRCA1 to regions of DNA damage.
Comment:
We observed that 11 HBOC patients with L1780P variant showed typical clinicopathological feature of patients with BRCA1 mutations. When we apply the ACMG standards and guideline for reclassification of L1780P, L1780P is a highly suspected of pathogenic varints of BRCA1. A previous study (Lee et al, 2010) also indicated that L1780P mutation causes adverse effects on cells in functional anlayses. Our re-classification according to the ACMG guidelines for L1780P variant published in Cancer Research and Treatment (Park et al, 2017, e-pub).
Comment:
Published functional studies demonstrate a damaging effect: absent or reduced protease sensitivity, binding activity and specificity, cell survival, and transcription activity (Hayes 2000, Lee 2010, Findlay 2018); Observed in multiple individuals of Korean ancestry with breast and/or ovarian cancer (Choi 2004, Han 2006, Jang 2012, Eoh 2016, Yoon 2016, Ryu 2017); Case control studies in Korean women suggest this variant is associated with hereditary breast and ovarian cancer and may be a pathogenic Korean founder variant (Park 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 5458T>C; This variant is associated with the following publications: (PMID: 20378548, 19491284, 15235020, 27124784, 29240602, 27383479, 30415210, 20516115, 15117986, 17100994, 16949048, 22217648, 15172985, 10811118, 28111427, 28781887, 29020732, 28364669, 27658390, 28288110, 27488874, 29770616, 30209399, 30765603, 30309222, 32019279, 30350268)
Comment:
The frequency of this variant in the general population, 0.000008 (2/251430 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported as a founder mutation in the Korean population (PMIDs: 28111427 (2017), 28364669 (2017), 30309222 (2019)). It has been found in individuals with breast and/or ovarian cancer (PMIDs: 115117986 (2004), 17100994 (2006), 22217648 (2012), 27124784 (2016), 27488874 (2017), 27658390 (2017), 28364669 (2017), 28111427 (2017), 29020732 (2018), 29240602 (2018), 30309222 (2019), 30350268 (2019), 32019279 (2020), 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA1), and 34645131 (2022)). Additionally, the variant has been reported in healthy individuals (PMIDs: 17100994 (2006), 22217648 (2012), and 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA1)). Functional studies describe the variant as having a strong impact on the BRCA1 gene that results in the loss of protein function (PMIDs: 20516115 (2010), 30209399 (2018), 30415210 (2018), 30765603 (2019), 31907386 (2020), 32803532 (2020), 32546644 (2020), and 33087888 (2021)). Based on the available information, this variant is classified as pathogenic.
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 10811118, 20378548, 20516115, 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: 55541). This missense change has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 15117986, 17100994, 22217648, 27124784, 27383479, 27488874, 27658390, 28111427, 28288110, 28364669, 29020732, 29770616). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs80357474, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1780 of the BRCA1 protein (p.Leu1780Pro).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain). | Pitiot AS | Clinical genetics | 2024 | PMID: 38922859 |
| Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer. | Lee JD | Cancers | 2022 | PMID: 35626017 |
| Clinicopathological Characterization of Double Heterozygosity for BRCA1 and BRCA2 Variants in Korean Breast Cancer Patients. | Bang YJ | Cancer research and treatment | 2022 | PMID: 34645131 |
| Integration of functional assay data results provides strong evidence for classification of hundreds of BRCA1 variants of uncertain significance. | Lyra PCM Jr | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 33087888 |
| 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 |
| Functional Categorization of BRCA1 Variants of Uncertain Clinical Significance in Homologous Recombination Repair Complementation Assays. | Bouwman P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2020 | PMID: 32546644 |
| Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant. | Park HS | Cancer research and treatment | 2020 | PMID: 32019279 |
| Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer. | Kim HK | Journal of human genetics | 2020 | PMID: 31907386 |
| Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
| Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. | Ryu JM | Breast cancer research and treatment | 2019 | PMID: 30350268 |
| Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review. | Kwon BS | Cancer research and treatment | 2019 | PMID: 30309222 |
| Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort. | Lee JS | Journal of medical genetics | 2018 | PMID: 30415210 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube. | Choi MC | Journal of gynecologic oncology | 2018 | PMID: 29770616 |
| Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer. | Choi MC | International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | 2018 | PMID: 29240602 |
| Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2. | Eoh KJ | Cancer research and treatment | 2018 | PMID: 29020732 |
| Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea. | Ryu JM | Breast (Edinburgh, Scotland) | 2017 | PMID: 28364669 |
| HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. | Davies H | Nature medicine | 2017 | PMID: 28288110 |
| Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. | Park JS | Cancer research and treatment | 2017 | PMID: 28111427 |
| Clinically Significant Unclassified Variants in BRCA1 and BRCA2 genes among Korean Breast Cancer Patients. | Yoon KA | Cancer research and treatment | 2017 | PMID: 27658390 |
| Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients. | Eoh KJ | Cancer research and treatment | 2017 | PMID: 27488874 |
| Evaluation of an amplicon-based next-generation sequencing panel for detection of BRCA1 and BRCA2 genetic variants. | Shin S | Breast cancer research and treatment | 2016 | PMID: 27383479 |
| Comparative analysis of BRCA1 and BRCA2 variants of uncertain significance in patients with breast cancer: a multifactorial probability-based model versus ACMG standards and guidelines for interpreting sequence variants. | Park KS | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 27124784 |
| Spectra of BRCA1 and BRCA2 mutations in Korean patients with breast cancer: the importance of whole-gene sequencing. | Jang JH | Journal of human genetics | 2012 | PMID: 22217648 |
| Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
| Toward classification of BRCA1 missense variants using a biophysical approach. | Rowling PJ | The Journal of biological chemistry | 2010 | PMID: 20378548 |
| Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer. | Han SH | Clinical genetics | 2006 | PMID: 17100994 |
| Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. | Choi DH | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2004 | PMID: 15117986 |
| Functional assay for BRCA1: mutagenesis of the COOH-terminal region reveals critical residues for transcription activation. | Hayes F | Cancer research | 2000 | PMID: 10811118 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80357474 ...
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Record last updated Oct 13, 2024
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