Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076327 | SCV000107351 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
| Ambry Genetics | RCV001013869 | SCV001174505 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | The p.Y656* pathogenic mutation (also known as c.1968C>G), located in coding exon 12 of the MSH2 gene, results from a C to G substitution at nucleotide position 1968. This changes the amino acid from a tyrosine to a stop codon within coding exon 12. This alteration has been identified in numerous kindreds from Lynch syndrome cohorts, several of whom meet Amsterdam and/or Bethesda criteria (Kohonen-Corish M et al. Am. J. Hum. Genet. 1996 Oct;59:818-24; Mangold E et al. Int. J. Cancer 2005 Sep;116:692-702; Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7; Sunga AY et al. Cancer Genet. 2017 Apr;212-213:1-7; Yurgelun MB et al. Gastroenterology, 2015 Sep;149:604-13.e20; Loizidou MA et al. PLoS One, 2014 Aug;9:e105501; Latham A et al. J Clin Oncol, 2019 02;37:286-295). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 | RCV001069113 | SCV001234260 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-08-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr656*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 8808596, 15849733, 16451135, 25133505, 28449805). ClinVar contains an entry for this variant (Variation ID: 90825). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003452869 | SCV004188047 | pathogenic | Lynch syndrome 1 | 2023-08-04 | 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. |