ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1907C>T (p.Ser636Leu)

dbSNP: rs431825288
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220348 SCV000275489 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-23 criteria provided, single submitter clinical testing The p.S636L variant (also known as c.1907C>T), located in coding exon 9 of the BRCA2 gene, results from a C to T substitution at nucleotide position 1907. The serine at codon 636 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001347842 SCV001542122 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 636 of the BRCA2 protein (p.Ser636Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231589). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV004767174 SCV005377306 uncertain significance not provided 2023-11-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2135C>T; This variant is associated with the following publications: (PMID: 32377563, 30755392, 29884841)

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