ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3632T>C (p.Leu1211Pro) (rs864622041)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215362 SCV000273358 likely pathogenic Hereditary cancer-predisposing syndrome 2017-12-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Structural Evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000206750 SCV000259176 pathogenic Lynch syndrome I 2015-11-24 reviewed by expert panel research
Invitae RCV000471873 SCV000551224 uncertain significance Lynch syndrome 2016-06-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1211 of the MSH6 protein (p.Leu1211Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 219294). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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