ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3992G>T (p.Arg1331Leu) (rs184131049)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239122 SCV000296882 uncertain significance Lynch syndrome 2015-10-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV001021599 SCV001183235 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-12 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001046197 SCV001210091 uncertain significance Hereditary nonpolyposis colon cancer 2019-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 1331 of the MSH6 protein (p.Arg1331Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs184131049, ExAC 0.01%). This variant has not been reported in the literature in individuals with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 252468). 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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