Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076367 | SCV000107393 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Invitae | RCV001854323 | SCV002230945 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-10-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 16405554). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile679Serfs*19) 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). |
Ambry Genetics | RCV002415561 | SCV002723008 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-20 | criteria provided, single submitter | clinical testing | The c.2035_2036delAT pathogenic mutation, located in coding exon 13 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 2035 to 2036, causing a translational frameshift with a predicted alternate stop codon (p.I679Sfs*19). This alteration has been previously identified in one individual of Japanese descent who had personal history of bladder and rectal cancer in addition to a liposarcoma, diagnosed at ages 31, 32, and 40, respectively. Analysis of the rectal and liposarcoma tumors using immunohistochemistry revealed loss of MSH2 protein (Hirata K et al. Am. J. Gastroenterol., 2006 Jan;101:193-6). 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. |