ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3923_3924insATCT

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825600 SCV000966943 likely pathogenic Lynch syndrome 2017-12-14 criteria provided, single submitter clinical testing The p.Pro1309fs variant in MSH6 has been reported in 2 individual with MSH6-asso ciated cancers (Haraldsdottir 2016, Hampel 2008) and was absent from large popul ation studies, though the ability of these studies to accurately detect indels m ay be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 1309 and leads to a prematu re termination codon 11 amino acids downstream. This termination codon occurs wi thin the terminal 50 bases of the second to last exon and is more likely to esca pe nonsense mediated decay (NMD), resulting in a truncated protein. Truncating v ariants downstream of this variant have been reported in individuals with Lynch syndrome. In summary, although additional studies are required to fully establis h its clinical significance, the p.Pro1309fs variant is likely pathogenic. ACMG/ AMP Criteria applied: PVS1_Strong; PM2; PS4_Supporting.

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