ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2935C>T (p.Arg979Cys) (rs80356970)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048019 SCV000076032 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 979 of the BRCA1 protein (p.Arg979Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs80356970, ExAC 0.01%). This variant has been reported in an individual/family with breast and/or ovarian cancer (PMID: 18273839). This variant is also known as 3054C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54727). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV000130686 SCV000185573 likely benign Hereditary cancer-predisposing syndrome 2019-08-14 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000433032 SCV000512297 likely benign not specified 2017-08-24 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000130686 SCV000688407 likely benign Hereditary cancer-predisposing syndrome 2016-09-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000433032 SCV000918750 uncertain significance not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2935C>T (p.Arg979Cys) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant was found in 6/246104 control chromosomes (gnomAD) at a frequency of 0.0000244, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). Multiple publications have cited the variant in affected individuals, however, with limited informatin (ie, lack of co-occurrence and cosegregation data). However, one reputable database that classifies the variant as "UV" reports the variant to co-occur with a pathogenic BRCA2 variant, c.771_775delTCAAA (p.Asn257LysfsX17 - scored DV by LCA), therefore, suggesting a potential benign impact. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Sharing Clinical Reports Project (SCRP) RCV000077531 SCV000109332 likely benign Breast-ovarian cancer, familial 1 2012-02-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077531 SCV000144588 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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