Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075182 | SCV000106173 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001854289 | SCV002223643 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-05-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 89708). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu460Argfs*31) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). |
Myriad Genetics, |
RCV003451020 | SCV004186373 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-20 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Ambry Genetics | RCV004019099 | SCV005033323 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-06 | criteria provided, single submitter | clinical testing | The c.1377delA pathogenic mutation, located in coding exon 12 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 1377, causing a translational frameshift with a predicted alternate stop codon (p.E460Rfs*31). This variant has been observed in at least one individual with a personal and/or family history that is consistent with Lynch syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |