ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2563C>A (p.Gln855Lys) (rs80357131)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689658 SCV000817321 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 855 of the BRCA1 protein (p.Gln855Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001340 SCV001158534 uncertain significance not specified 2019-06-10 criteria provided, single submitter clinical testing The BRCA1 c.2563C>A; p.Gln855Lys variant, to our knowledge, is not reported in the medical literature or gene-specific databases. However, another variant in the same codon, p.Gln855Pro, is reported in the literature in an individual with breast cancer (Momozawa 2018). The p.Gln855Lys variant is reported in the ClinVar database (Variation ID: 569114), but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The amino acid at this position is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the variant is uncertain at this time. References: Momozawa Y et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018 Oct 4;9(1):4083.

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