ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.818G>T (p.Gly273Val) (rs769610487)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232347 SCV000283858 uncertain significance Hereditary nonpolyposis colon cancer 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 273 of the MSH6 protein (p.Gly273Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs769610487, ExAC 0.002%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 237215). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000561246 SCV000669949 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000561246 SCV000685521 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-15 criteria provided, single submitter clinical testing
Mendelics RCV000708857 SCV000837871 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000582421 SCV000691921 uncertain significance not specified no assertion criteria provided clinical testing

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