ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1773dup (p.Ser592Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV003584437 SCV004359249 pathogenic Hereditary cancer-predisposing syndrome 2023-07-10 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 16 of the MLH1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with MLH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MLH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV004011496 SCV004827046 pathogenic Lynch syndrome 2023-05-03 criteria provided, single submitter clinical testing The c.1773dup (p.Ser592*) variant of the MLH1 gene results in a premature termination codon that is predicted to lead to absent or truncated protein product. Loss-of-function variants in MLH1 gene are known to be pathogenic (PMID: 14635101, 15942939, 16955466, 15713769, 24362816, 33468175). Truncating variants downstream of this variant are reported to be pathogenic in the literature (PMID: 8571956, 12810663, 15849733, 20459533) and ClinVar (ClinVar ID: 89888, 89889). This variant is absent in the general population database (gnomAD). Therefore, the c.1773dup (p.Ser592*) variant in the MLH1 gene is classified as pathogenic.

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