Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076740 | SCV000107777 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV000165329 | SCV000216052 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-19 | criteria provided, single submitter | clinical testing | The p.E290* pathogenic mutation (also known as c.868G>T), located in coding exon 5 of the MSH2 gene, results from a G to T substitution at nucleotide position 868. This changes the amino acid from a glutamic acid to a stop codon within coding exon 5. This alteration has been previously reported in families meeting Amsterdam II criteria. One individual with this mutation had a personal history of endometrial cancer; another was reported to have a tumor with absent MSH2 by IHC analysis (De Lellis L et al. PLoS ONE 2013 Nov;8:e81194; Bozzao C et al. Cancer 2011 Sep;117:4325-35). 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. |
| Fulgent Genetics, |
RCV000763488 | SCV000894274 | pathogenic | Lynch syndrome 1; Mismatch repair cancer syndrome 1; Muir-Torré syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001854340 | SCV002239467 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-04-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Lynch syndrome (PMID: 21387278, 29025352). ClinVar contains an entry for this variant (Variation ID: 91235). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu290*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). |
| Myriad Genetics, |
RCV003452971 | SCV004187921 | pathogenic | Lynch syndrome 1 | 2023-07-28 | 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 | RCV003452971 | SCV004196878 | pathogenic | Lynch syndrome 1 | 2022-12-06 | criteria provided, single submitter | clinical testing |