Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076164 | SCV000107181 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
A. |
RCV000076164 | SCV000914301 | pathogenic | Lynch syndrome | 2019-01-30 | criteria provided, single submitter | research | |
Invitae | RCV001064013 | SCV001228886 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-03-10 | 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 clinical features of Lynch syndrome (PMID: 12624141, 28874130, 17312306). ClinVar contains an entry for this variant (Variation ID: 90668). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu483*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
Clinical Genetics and Genomics, |
RCV001269568 | SCV001449646 | pathogenic | not provided | 2016-04-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002390225 | SCV002701552 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-17 | criteria provided, single submitter | clinical testing | The p.E483* pathogenic mutation (also known as c.1447G>T), located in coding exon 9 of the MSH2 gene, results from a G to T substitution at nucleotide position 1447. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation has been reported in multiple HNPCC families of various ethnicities (Parc Y et al. J. Med. Genet. 2003 Mar;40:208-13; Lagerstedt Robinson K et al. J. Natl. Cancer Inst. 2007 Feb;99:291-9; Valentin MD et al. Fam. Cancer 2011 Dec;10:641-7; Bonadona V et al. JAMA 2011 Jun;305:2304-10). 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. |
Color Diagnostics, |
RCV002390225 | SCV004356685 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-17 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 9 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome (PMID: 12624141, 17312306, 21681552, 26437257, 28874130). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |