ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2288C>T (p.Ala763Val) (rs144412585)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160609 SCV000211206 uncertain significance not provided 2018-04-12 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.2288C>T at the cDNA level, p.Ala763Val (A763V) at the protein level, and results in the change of an Alanine to a Valine (GCA>GTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ala763Val was not observed in large population cohorts (Lek 2016). This variant is located in the ATPase Domain (L?tzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Ala763Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000218725 SCV000273937 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Other data supporting pathogenic classification,Insufficient or conflicting evidence
Invitae RCV000456427 SCV000548276 uncertain significance Hereditary nonpolyposis colon cancer 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 763 of the MSH2 protein (p.Ala763Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 182578). 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 disruptive, 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.
Color RCV000218725 SCV000904007 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-23 criteria provided, single submitter clinical testing

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