ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2300C>T (p.Thr767Ile) (rs587781462)

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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 RCV000129397 SCV000184163 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Other data supporting pathogenic classification,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Counsyl RCV000410431 SCV000488090 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2015-12-23 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501569 SCV000592603 uncertain significance not specified 2014-05-23 criteria provided, single submitter clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000622945 SCV000740675 pathogenic Lynch syndrome I 2018-03-09 reviewed by expert panel curation Class 5 - Pathogenic Classification using multifactorial probability: 0.993
Invitae RCV000477388 SCV000551179 uncertain significance Hereditary nonpolyposis colon cancer 2018-05-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 767 of the MSH6 protein (p.Thr767Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 141058). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000501569 SCV000601529 uncertain significance not specified 2017-02-23 criteria provided, single submitter clinical testing

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