ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.376G>A (p.Gly126Ser) (rs767371843)

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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 RCV000166502 SCV000217301 uncertain significance Hereditary cancer-predisposing syndrome 2014-10-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes),Co-occurence with mutation in same gene (phase unknown)
Invitae RCV000199020 SCV000254419 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 126 of the MSH2 protein (p.Gly126Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs767371843, ExAC 0.001%). This variant has been reported in individuals affected with Lynch syndrome-associated tumors (PMID: 24278394, 28449805). However, one of these individuals also carried another variant in the MSH2 gene (PMID: 24278394). ClinVar contains an entry for this variant (Variation ID: 186849). 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.
Fulgent Genetics,Fulgent Genetics RCV000515190 SCV000611401 uncertain significance Lynch syndrome I; Turcot syndrome; Muir-Torré syndrome 2017-05-23 criteria provided, single submitter clinical testing

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