Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075584 | SCV000106581 | uncertain significance | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Insufficient evidence: premature termination codon outside of known functional domain; Nonsense variant after codon 743 in MLH1 = VUS |
Invitae | RCV001854299 | SCV002229931 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-09-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MLH1 protein in which other variant(s) (p.Lys751Serfs*3) have been determined to be pathogenic (PMID: 8797773, 18566915, 18931482, 24802709, 27295708). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this premature translational stop signal affects MLH1 function (PMID: 20533529). ClinVar contains an entry for this variant (Variation ID: 90098). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 20233461). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr750*) in the MLH1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 7 amino acid(s) of the MLH1 protein. |
Myriad Genetics, |
RCV003451118 | SCV004186456 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |