Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076132 | SCV000107147 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV000573345 | SCV000676095 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | clinical testing | The p.E452* variant (also known as c.1354G>T), located in coding exon 8 of the MSH2 gene, results from a G to T substitution at nucleotide position 1354. This changes the amino acid from a glutamic acid to a stop codon within coding exon 8. This alteration was detected in a patient with colon cancer at age 44, whose tumor demonstrated absent MSH2 protein staining on immunohistochemistry (IHC) (Julié C et al. Am. J. Gastroenterol., 2008 Nov;103:2825-35). 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 | RCV000791561 | SCV000930817 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-12-24 | 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: 90636). This premature translational stop signal has been observed in individual(s) with colon cancer (PMID: 18759827). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu452*) 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). |
Myriad Genetics, |
RCV003452825 | SCV004189614 | pathogenic | Lynch syndrome 1 | 2023-10-12 | 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. |