Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075230 | SCV000106223 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Genetics and Molecular Pathology, |
RCV000075230 | SCV002556560 | pathogenic | Lynch syndrome | 2020-05-14 | criteria provided, single submitter | clinical testing | The MLH1:c.150dup variant is a single nucleotide insertion which introduces a frameshift at position 51 in the protein. The variant has been reported in the literature in association with disease (PMID: 9886275, PMID: 15849733). It is absent from population databases (PM2). The variant is described in ClinVar and InSiGHT as pathogenic and HGMD (2020.1) as disease causing (PP5). This frameshift variant is in exon 2 of 19 and leads to a premature termination codon 1 amino acid downstream, truncating a significant proportion of the wild type MLH1 protein which is 756 amino acids in length (PVS1). Premature truncation at codon 52 is predicted to result in a loss of the ATPase domain, MutS homologs interaction domain, EXO1interaction domain and PMS2/MLH3/PMS2 interaction domain which is likely to have a detrimental effect on the protein function. The MLH1:c.150dup variant is classified as PATHOGENIC (PVS1,PM2,PP5). |