Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075702 | SCV000106705 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV003153350 | SCV000543531 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-06-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant has not been reported in the literature in individuals with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 90213). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu135Glnfs*24) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV001021735 | SCV001183386 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-24 | criteria provided, single submitter | clinical testing | The c.404_407delTGAA pathogenic mutation, located in coding exon 5 of the MLH1 gene, results from a deletion of 4 nucleotides at nucleotide positions 404 to 407, causing a translational frameshift with a predicted alternate stop codon (p.L135Qfs*24). 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. |
| Myriad Genetics, |
RCV003455998 | SCV004186471 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-13 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003455998 | SCV004190608 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-09-09 | criteria provided, single submitter | clinical testing |