Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076699 | SCV000107734 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV000164791 | SCV000215470 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-24 | criteria provided, single submitter | clinical testing | The c.746delA pathogenic mutation, located in coding exon 4 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 746, causing a translational frameshift with a predicted alternate stop codon (p.K249Rfs*5). To date, this mutation has been observed in five French HNPCC families, including in a proband diagnosed with colorectal cancer at age 30 and a family history meeting Amsterdam criteria (Bonadona V et al. JAMA. 2011 Jun 8;305(22):2304-10; Rey JM et al. Cancer Genet Cytogenet. 2004 Dec;155(2):149-51). 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. |
| Invitae | RCV001380410 | SCV001578475 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-09-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been observed in individual(s) with Lynch syndrome (PMID: 15571801, 21642682). ClinVar contains an entry for this variant (Variation ID: 91195). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys249Argfs*5) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
| Myriad Genetics, |
RCV003452964 | SCV004188997 | pathogenic | Lynch syndrome 1 | 2023-07-27 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Cancer Genomics Lab, |
RCV000164791 | SCV004011749 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-13 | no assertion criteria provided | clinical testing |