ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.161G>C (p.Gly54Ala) (rs63751098)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160718 SCV000212983 likely benign Hereditary cancer-predisposing syndrome 2018-02-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification,Intact protein function observed in appropriate functional assay(s)
Color RCV000160718 SCV000903487 benign Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing
Counsyl RCV000662366 SCV000784756 likely benign Hereditary nonpolyposis colorectal cancer type 5 2017-01-25 criteria provided, single submitter clinical testing
GeneDx RCV000212627 SCV000211352 likely benign not specified 2017-12-06 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.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074671 SCV000107874 likely benign Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability 0.001-0.049
Invitae RCV000630046 SCV000751002 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 54 of the MSH6 protein (p.Gly54Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs63751098, ExAC 0.01%). This variant has been reported in individuals affected with colorectal cancer and ovarian cancer (PMID: 14520694, 23047549). ClinVar contains an entry for this variant (Variation ID: 89208). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) and algorithms developed specifically for the MSH6 gene (PMID: 22290698, 23621914) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212627 SCV000601510 likely benign not specified 2017-02-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759127 SCV000888245 likely benign not provided 2018-05-04 criteria provided, single submitter clinical testing

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