ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.919G>T (p.Val307Phe)

dbSNP: rs1672956447
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Sema4, Sema4 RCV002257139 SCV002526757 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter curation
Ambry Genetics RCV002257139 SCV002687494 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-12 criteria provided, single submitter clinical testing The p.V307F variant (also known as c.919G>T), located in coding exon 5 of the MSH2 gene, results from a G to T substitution at nucleotide position 919. The valine at codon 307 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. In addition, this alteration is predicted to be borderline deleterious by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094210 SCV003014808 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-08-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 307 of the MSH2 protein (p.Val307Phe). 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. Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt MSH2 protein function. ClinVar contains an entry for this variant (Variation ID: 1692298). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency).

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