ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.2157dup (p.Val720fs)

dbSNP: rs587778984
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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) RCV000075561 SCV000106558 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon with functional domain
Labcorp Genetics (formerly Invitae), Labcorp RCV003593882 SCV004293477 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-12-19 criteria provided, single submitter clinical testing This variant disrupts a region of the MLH1 protein in which other variant(s) (p.Tyr750*, p.Lys751Serfs*3) have been determined to be pathogenic (PMID: 8797773, 18566915, 18931482, 24802709, 27295708; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Val720Cysfs*3) in the MLH1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the MLH1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 21286823, 21615986). ClinVar contains an entry for this variant (Variation ID: 90075). For these reasons, this variant has been classified as Pathogenic.

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