ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3416G>T (p.Gly1139Val) (rs1316409501)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000499888 SCV000592639 likely pathogenic Lynch syndrome 2013-06-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563961 SCV000673982 likely pathogenic Hereditary cancer-predisposing syndrome 2018-11-27 criteria provided, single submitter clinical testing Well-characterized mutation at same position;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Other data supporting pathogenic classification
Invitae RCV001211743 SCV001383297 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-05-31 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 1139 of the MSH6 protein (p.Gly1139Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 433923). 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.

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