ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.484G>C (p.Val162Leu) (rs55816927)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223399 SCV000275461 likely benign Hereditary cancer-predisposing syndrome 2019-02-26 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
GeneDx RCV000237044 SCV000292903 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.484G>C at the cDNA level, p.Val162Leu (V162L) at the protein level, and results in the change of a Valine to a Leucine (GTG>CTG). Using alternate nomenclature, this variant would be defined as BRCA1 603G>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Val162Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the BRD7 binding domain (Harte 2010). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Val162Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Counsyl RCV000112717 SCV000785460 uncertain significance Breast-ovarian cancer, familial 1 2017-08-15 criteria provided, single submitter clinical testing
Color Health, Inc RCV000223399 SCV000909410 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-07 criteria provided, single submitter clinical testing
Invitae RCV001342417 SCV001536348 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-02-19 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 162 of the BRCA1 protein (p.Val162Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. 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. ClinVar contains an entry for this variant (Variation ID: 55303). 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112717 SCV000145596 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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