Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075493 | SCV000106489 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV000524268 | SCV000543526 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-06-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 90009). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys680*) 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). |
| Department of Pathology and Laboratory Medicine, |
RCV000075493 | SCV000592437 | pathogenic | Lynch syndrome | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV000573665 | SCV000669582 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-09 | criteria provided, single submitter | clinical testing | The p.C680* pathogenic mutation (also known as c.2040C>A), located in coding exon 18 of the MLH1 gene, results from a C to A substitution at nucleotide position 2040. This changes the amino acid from a cysteine to a stop codon within coding exon 18. This mutation has been reported in multiple HNPCC families in the literature (Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7; De Lellis L et al. PLoS ONE 2013 Nov;8:e81194). This alteration has also been identified in at least one patient with a personal and family history of breast and/or ovarian cancer (Maxwell KN et al. Am J Hum Genet, 2016 May;98:801-817). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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, |
RCV003451097 | SCV004186296 | 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. |
| Baylor Genetics | RCV003451097 | SCV004193020 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-03-06 | criteria provided, single submitter | clinical testing |