ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.184C>A (p.Arg62Ser) (rs876659508)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219210 SCV000276061 likely benign Hereditary cancer-predisposing syndrome 2016-10-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,in silico models in agreement (benign)
GeneDx RCV000421764 SCV000517972 likely benign not specified 2016-06-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000697068 SCV000825658 uncertain significance Hereditary nonpolyposis colon cancer 2018-05-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 62 of the MSH6 protein (p.Arg62Ser). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and serine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 232033). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 RCV000219210 SCV000903697 likely benign Hereditary cancer-predisposing syndrome 2018-09-07 criteria provided, single submitter clinical testing

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