Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076448 | SCV000107477 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV000223378 | SCV000273589 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-03 | criteria provided, single submitter | clinical testing | The p.G759* pathogenic mutation (also known as c.2275G>T), located in coding exon 14 of the MSH2 gene, results from a G to T substitution at nucleotide position 2275. This changes the amino acid from a glycine to a stop codon within coding exon 14. This variant has been identified in a proband(s) whose Lynch syndrome-associated tumor demonstrated loss of MSH2 expression by immunohistochemistry (Stormorken AT et al. J Clin Oncol. 2005 Jul 20;23(21):4705-12; Grindedal EM et al. Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2460-7; Sjursen W et al. J Med Genet. 2010 Sep;47(9):579-85). 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 | RCV000798392 | SCV000938008 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-08 | 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: 90946). This premature translational stop signal has been observed in individual(s) with Lynch syndrome and prostrate cancer (PMID: 15342696, 16034045, 19723918, 27601186, 28514183). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly759*) 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, |
RCV003452903 | SCV004187933 | 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. |