ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1709A>G (p.Tyr570Cys) (rs587779963)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115506 SCV000149415 uncertain significance not provided 2014-01-08 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1709A>G at the cDNA level, p.Tyr570Cys (Y570C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAT>TGT) in exon 11. This variant has not, to our knowledge, been published in the literature as either a mutation or a benign polymorphism. MSH2 Tyr570Cys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Variant Server. This variant is a non-conservative amino acid substitution, altering a position that is well conserved throughout evolution and is located within the lever domain (LŸtzen 2008). Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on the currently available information, we consider MSH2 Tyr570Cys to be a variant of unknown significance. The variant is found in HEREDICANCER panel(s).
Invitae RCV000555354 SCV000625301 uncertain significance Hereditary nonpolyposis colon cancer 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 570 of the MSH2 protein (p.Tyr570Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs587779963, ExAC 0.002%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 127633). 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.
Ambry Genetics RCV000574691 SCV000662247 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-31 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000574691 SCV000684968 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-06 criteria provided, single submitter clinical testing

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