Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076450 | SCV000107480 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV000491006 | SCV000580554 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-27 | criteria provided, single submitter | clinical testing | The p.W764* pathogenic mutation (also known as c.2291G>A), located in coding exon 14 of the MSH2 gene, results from a G to A substitution at nucleotide position 2291. This changes the amino acid from a tryptophan to a stop codon within coding exon 14. This mutation has been reported in an individual with early onset colon cancer whose tumor showed absence of MSH2 protein expression (Nagasaka T et al. Cancer Res. 2010 Apr; 70(8):3098-108). This alteration has also been reported in an individual meeting Amsterdam II criteria with early onset colon cancer and hepatocellular carcinoma showing microsatellite instability and loss of MSH2 protein expression (Casper M et al. Scand. J. Gastroenterol. 2013 Mar; 48(3):344-51). 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 | RCV000694856 | SCV000823318 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp764*) 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 colorectal cancer and suspected Lynch syndrome (PMID: 20388775, 25980754). ClinVar contains an entry for this variant (Variation ID: 90948). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003452904 | SCV004188032 | pathogenic | Lynch syndrome 1 | 2023-08-08 | 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. |