Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076531 | SCV000107546 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
ARUP Laboratories, |
RCV001001138 | SCV001158285 | pathogenic | not specified | 2019-03-13 | criteria provided, single submitter | clinical testing | The MSH2 c.263_264delTT; p.Phe88fs variant (rs267607920) has been described in association with hereditary nonpolyposis colorectal cancer (Bujalkova 2008). It contains an entry in ClinVar (Variation ID: 91029) and is absent from general population databases (Exome Variant Server and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Bujalkova M et al. Multiplex SNaPshot genotyping for detecting loss of heterozygosity in the mismatch-repair genes MLH1 and MSH2 in microsatellite-unstable tumors. Clin Chem. 2008 Nov;54(11):1844-54. |
Invitae | RCV001383025 | SCV001582033 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-08-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 91029). This variant is also known as c.261_262delTT. This premature translational stop signal has been observed in individual(s) with a Lynch syndrome-associated cancer (PMID: 18772310). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe88Cysfs*11) 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, |
RCV003452930 | SCV004186898 | pathogenic | Lynch syndrome 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |