Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076596 | SCV000107630 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV000571607 | SCV000669702 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-08-02 | criteria provided, single submitter | clinical testing | The c.408delT pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 408, causing a translational frameshift with a predicted alternate stop codon. This mutation has been reported in multiple families meeting Amsterdam criteria for Lynch syndrome (Miyaki M et al. J. Mol. Med., 1995 Oct;73:515-20; Bai YQ et al. Int. J. Cancer, 1999 Aug;82:512-5). 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 | RCV000823518 | SCV000964379 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-03-09 | 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: 91094). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 8581513, 27433846). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe136Leufs*38) 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, |
RCV003452939 | SCV004186780 | 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. |