Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
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, |
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. |