Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076257 | SCV000107277 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV002399460 | SCV002714180 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | clinical testing | The p.Q574* pathogenic mutation (also known as c.1720C>T), located in coding exon 11 of the MSH2 gene, results from a C to T substitution at nucleotide position 1720. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This alteration has been reported in multiple patients with features of Lynch syndrome (Mangold E et al. Int J Cancer, 2005 Sep;116:692-702; Nagasaka T et al. Cancer Res, 2010 Apr;70:3098-108). 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. |
Myriad Genetics, |
RCV003452853 | SCV004186868 | pathogenic | Lynch syndrome 1 | 2023-08-03 | 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. |
Color Diagnostics, |
RCV002399460 | SCV004356698 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-20 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 11 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 or suspected Lynch syndrome (PMID: 15849733, 18550572, 27064304), or breast cancer (PMID: 27153395). 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. |