Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075674 | SCV000106676 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV001230876 | SCV001403376 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-08-18 | 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 observed in an individual affected with clinical features of Lynch syndrome (PMID: 10829038). ClinVar contains an entry for this variant (Variation ID: 90186). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr126*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002345379 | SCV002623306 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-09-11 | criteria provided, single submitter | clinical testing | The p.Y126* pathogenic mutation (also known as c.378C>G), located in coding exon 4 of the MLH1 gene, results from a C to G substitution at nucleotide position 378. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. This variant has been reported in multiple Lynch syndrome families to date (Wang Q et al. Hum. Genet.;105:79-85; van Lier MG et al. J. Pathol., 2012 Apr;226:764-74; Niskakoski A et al. Int. J. Cancer, 2013 Dec;133:2596-608). 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. |