ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.150dup (p.Val51fs)

dbSNP: rs63749956
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) 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, SA 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).

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