Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076700 | SCV000107735 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV000491026 | SCV000580471 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-20 | criteria provided, single submitter | clinical testing | The p.Q252* pathogenic mutation (also known as c.754C>T), located in coding exon 4 of the MSH2 gene, results from a C to T substitution at nucleotide position 754. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This alteration has been reported in multiple individuals with either early onset colorectal cancer or meeting Bethesda criteria (Barnetson RA et al. N. Engl. J. Med. 2006 Jun;354(26):2751-63; Farrington SM et al. Am. J. Hum. Genet. 1998 Sep; 63(3):749-59; Mangold E et al. Int. J. Cancer 2005 Sep;116(5):692-702; Liu Be et al. Nat. Med. 1995 Apr;1(4):348-52). 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 | RCV000808434 | SCV000948543 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-09-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 91196). This premature translational stop signal has been observed in individual(s) with Lynch syndrome-related cancer (PMID: 7585065, 15849733, 16807412). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln252*) 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). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003452965 | SCV004187005 | pathogenic | Lynch syndrome 1 | 2023-07-27 | 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. |