ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1021T>C (p.Cys341Arg) (rs55833327)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226133 SCV000283161 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 341 of the BRCA2 protein (p.Cys341Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs55833327, ExAC 0.02%). This variant has been reported in an individual affected with breast cancer (PMID: 28288110). ClinVar contains an entry for this variant (Variation ID: 236828). 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.
GeneDx RCV000443327 SCV000518223 likely benign not specified 2017-10-23 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000732589 SCV000600457 uncertain significance not provided 2019-04-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000443327 SCV000602792 uncertain significance not specified 2016-10-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000510111 SCV000608140 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-21 criteria provided, single submitter clinical testing The p.C341R variant (also known as c.1021T>C), located in coding exon 9 of the BRCA2 gene, results from a T to C substitution at nucleotide position 1021. The cysteine at codon 341 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000732589 SCV000860562 uncertain significance not provided 2018-04-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000510111 SCV001348877 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000443327 SCV001437369 uncertain significance not specified 2020-09-28 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1021T>C (p.Cys341Arg) results in a non-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 allele was found at a frequency of 1.2e-05 in 247644 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1021T>C has been reported in the literature in at-least one individual affected with breast cancer (Davies_2018). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=6, likely benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

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