ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2271C>T (p.Thr757=) (rs142172006)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162764 SCV000213241 likely benign Hereditary cancer-predisposing syndrome 2014-12-08 criteria provided, single submitter clinical testing
Color RCV000162764 SCV000685273 likely benign Hereditary cancer-predisposing syndrome 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000421153 SCV000513690 likely benign not specified 2017-09-15 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.
Integrated Genetics/Laboratory Corporation of America RCV000589413 SCV000695805 uncertain significance not provided 2016-01-04 criteria provided, single submitter clinical testing Variant summary: The variant of interest involves the alteration of a non-conserved nucleotide and results in a synonymous change. Mutation taster predicts a disease causing outcome for this substitution but 5/5 in silico tools via Alamut predict no significant impact on splice donor and acceptor sites. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.00082% which does not exceed the maximal expected allele frequency of a disease causing MSH6 allele (0.014%). To our knowledge, the variant was not reported in HNPCC spectrum patients and in vivo/vitro studies to describe the functional impact of the variant were not reported in the literature at the time of its evaluation either. An internal sample carrying this variant also carries a possible risk variant CHEK2 p.Ile157Thr, further supporting a possible benign outcome for this variant. Based on the synonymous nature of this substitution it is classified as VUS-Possibly Benign.
Invitae RCV000204330 SCV000260261 likely benign Hereditary nonpolyposis colon cancer 2017-12-19 criteria provided, single submitter clinical testing
PreventionGenetics RCV000589413 SCV000805860 likely benign not provided 2017-12-27 criteria provided, single submitter clinical testing

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