Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076746 | SCV000107783 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001854341 | SCV002236751 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-05-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 15849733). ClinVar contains an entry for this variant (Variation ID: 91241). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys301*) 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). |
Ambry Genetics | RCV002371917 | SCV002686315 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-21 | criteria provided, single submitter | clinical testing | The p.K301* pathogenic mutation (also known as c.901A>T), located in coding exon 5 of the MSH2 gene, results from an A to T substitution at nucleotide position 901. This changes the amino acid from a lysine to a stop codon within coding exon 5. This mutation was seen in patient with colorectal cancer that showed high microsatellite instability (MSI-H) and loss of MSH2 protein staining on IHC, with a family history meeting Bethesda criteria (Mangold E et al. J Pathol, 2005 Dec;207:385-95; Mangold E et al. Int J Cancer, 2005 Sep;116:692-702). 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. |
Revvity Omics, |
RCV003144124 | SCV003831409 | likely pathogenic | not provided | 2022-06-28 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003452974 | SCV004188092 | pathogenic | Lynch syndrome 1 | 2023-07-28 | 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. |