Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075309 | SCV000106303 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV002399444 | SCV002704236 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-19 | criteria provided, single submitter | clinical testing | The p.E558* pathogenic mutation (also known as c.1672G>T), located in coding exon 15 of the MLH1 gene, results from a G to T substitution at nucleotide position 1672. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This mutation has been reported in multiple individuals from families with HNPCC (Wang Q et al. Hum. Genet.;105:79-85; Kurzawski G et al. J. Biochem. Biophys. Methods, 2002 Mar;51:89-100; Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7; Mangold E et al. Int. J. Cancer, 2005 Sep;116:692-702). One study also proposed that this particular alteration significantly alters MLH1 splicing (Rhine CL et al. PLoS Genet., 2018 03;14:e1007231). 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. |