Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076061 | SCV000107075 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing a premature termination codon |
Ambry Genetics | RCV000490977 | SCV000580551 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-09 | criteria provided, single submitter | clinical testing | The p.Q402* pathogenic mutation (also known as c.1204C>T), located in coding exon 7 of the MSH2 gene, results from a C to T substitution at nucleotide position 1204. This changes the amino acid from a glutamine to a stop codon within coding exon 7. This mutation has been identified in several families with HNPCC/Lynch syndrome, including an Italian patient with pancreatic cancer (Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7; Gargiulo S et al. Fam. Cancer 2009;8:547-53; Moussa SA et al. Int J Colorectal Dis 2011 Apr;26:455-67; Ikenoue T et al. J Hum Genet, 2019 Dec;64:1187-1194). Of note, this alteration is also designated as Q402X and p.Gln402X in published literature. 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 | RCV001071140 | SCV001236428 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-01-28 | 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: 90565). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 16451135, 19728162, 21311894). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln402*) 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). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469004 | SCV002765984 | pathogenic | Hereditary nonpolyposis colon cancer | 2022-11-14 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.1204C>T (p.Gln402X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251442 control chromosomes (gnomAD). c.1204C>T has been reported in the literature in individuals affected with Lynch Syndrome and pancreatic cancer (e.g. Moussa_2011, Ikenoue_2019, Gargiulo_2009). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Myriad Genetics, |
RCV003452807 | SCV004188142 | pathogenic | Lynch syndrome 1 | 2023-07-31 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |