Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076280 | SCV000107301 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Invitae | RCV000524359 | SCV000548142 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-07-01 | criteria provided, single submitter | clinical testing | This sequence change inserts 1 nucleotide in exon 12 of the MSH2 mRNA (c.1771_1772insA), causing a frameshift at codon 591. This creates a premature translational stop signal (p.Pro591Hisfs*7) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with Lynch syndrome (PMID: 12362047). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV001013055 | SCV001173592 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-09-30 | criteria provided, single submitter | clinical testing | The c.1771_1772insA pathogenic mutation, located in coding exon 12 of the MSH2 gene, results from an insertion of one nucleotide at position 1771, causing a translational frameshift with a predicted alternate stop codon (p.P591Hfs*7). This mutation has been previously identified in a Polish cohort of HNPPC/Lynch syndrome kindreds (Kurzawski G et al. J. Med. Genet. 2002 Oct;39:E65; Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7; Kurzawski G et al. J. Biochem. Biophys. Methods. 2002 Mar;51:89-100; Kurzawski G. Hered Cancer Clin Pract, 2006 Dec;4:197-205). 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. |