Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076646 | SCV000107681 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV000565347 | SCV000676085 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-23 | criteria provided, single submitter | clinical testing | The c.587delC pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 587, causing a translational frameshift with a predicted alternate stop codon (p.P196Qfs*18). This pathogenic mutation has been reported in individuals with clinical histories consistent with Lynch syndrome and Muir-Torre syndrome (Hampel H et al. N. Engl. J. Med. 2005 May; 352(18):1851-60; South CD et al. J. Natl. Cancer Inst. 2008 Feb; 100(4):277-81). Of note, this alteration is also designated as c.586delC in published literature. 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 | RCV002514359 | SCV003524574 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-07-29 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with MSH2-related conditions (PMID: 15872200). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 91142). This variant is also known as c.586delC. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro196Glnfs*18) 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, |
RCV003452953 | SCV004186860 | pathogenic | Lynch syndrome 1 | 2023-07-27 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |