ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2295C>G (p.Cys765Trp) (rs63750985)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570110 SCV000670028 likely pathogenic Hereditary cancer-predisposing syndrome 2019-04-08 criteria provided, single submitter clinical testing Structural Evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Other data supporting pathogenic classification
Invitae RCV001063838 SCV001228701 uncertain significance Hereditary nonpolyposis colon cancer 2019-05-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 765 of the MSH6 protein (p.Cys765Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with colon cancer and endometrial cancer (PMID: 16418736). ClinVar contains an entry for this variant (Variation ID: 89265). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be deleterious (PMID: 22290698, 23621914). However, this prediction has not been confirmed by published functional studies and its 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.

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