Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076063 | SCV000107077 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing a premature termination codon |
Ambry Genetics | RCV002354267 | SCV002659744 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-03-15 | criteria provided, single submitter | clinical testing | The p.Y405* pathogenic mutation (also known as c.1215C>A), located in coding exon 7 of the MSH2 gene, results from a C to A substitution at nucleotide position 1215. This changes the amino acid from a tyrosine to a stop codon within coding exon 7. This alteration was reported in multiple Lynch syndrome families (Kurzawski G et al. Clin Genet, 2006 Jan;69:40-7; Dominguez-Valentin M et al. Hered Cancer Clin Pract, 2013 Dec;11:1; Jun SY et al. Oncotarget, 2017 Mar;8:21483-21500; Rossi BM et al. BMC Cancer, 2017 Sep;17:623; De Lellis L et al. PLoS One, 2013 Nov;8:e81194). 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. |
Color Diagnostics, |
RCV002354267 | SCV004356665 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 7 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome (PMID: 16451135, 20305446, 24278394, 31332305). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |