ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.668A>G (p.Asn223Ser) (rs587779316)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500727 SCV000592574 likely benign not specified 2015-03-11 criteria provided, single submitter clinical testing
Color RCV000579865 SCV000685514 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-21 criteria provided, single submitter clinical testing
Invitae RCV000629721 SCV000750677 uncertain significance Hereditary nonpolyposis colon cancer 2017-12-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 223 of the MSH6 protein (p.Asn223Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals in the Leiden Open-source Variation Database (PMID: 21520333). However, in one of these individuals a pathogenic allele was also identified in MSH6, which suggests that this c.668A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 89554). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be tolerated (PMID: 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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