Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018091 | SCV004847757 | likely pathogenic | Lynch syndrome | 2019-05-08 | criteria provided, single submitter | clinical testing | The p.Glu544LysfsX27 variant in MSH6 has not been previously reported in individuals with Lynch Syndrome and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 544 and leads to a premature termination codon 27 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MSH6 gene is an established disease mechanism in individuals with Lynch syndrome. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP criteria applied: PVS1, PM2. |