Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075207 | SCV000106198 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV000553242 | SCV000625063 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-02-23 | 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 been reported in an individual affected with Lynch syndrome (PMID: 17653898). ClinVar contains an entry for this variant (Variation ID: 89733). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg472Thrfs*6) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
| MGZ Medical Genetics Center | RCV002288567 | SCV002581181 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2021-10-08 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV002288567 | SCV004186573 | 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 | RCV004019100 | SCV005033243 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-21 | criteria provided, single submitter | clinical testing | The c.1415_1416delGA pathogenic mutation, located in coding exon 13 of the MLH1 gene, results from a deletion of two nucleotides at nucleotide positions 1415 to 1416, causing a translational frameshift with a predicted alternate stop codon (p.R472Tfs*6). This variant was reported in multiple individuals with features consistent with Lynch syndrome (Rahner N et al. Acta Oncol, 2007;46:763-9; Morak M et al. Eur J Hum Genet, 2019 Dec;27:1808-1820). 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. |