Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018088 | SCV004847752 | likely pathogenic | Lynch syndrome | 2019-05-08 | criteria provided, single submitter | clinical testing | The p.Cys256MetfsX51 variant in MLH1 has not been previously been reported in individuals with Lynch syndrome-related cancers 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 256 and leads to a premature termination codon 51 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MLH1 gene is an established disease mechanism in autosomal dominant 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. |