Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076682 | SCV000107717 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV000627708 | SCV000284177 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-08-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala230Serfs*2) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 8581513, 21868491, 25200962). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 91178). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000491369 | SCV000580466 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-12 | criteria provided, single submitter | clinical testing | The c.687dupA pathogenic mutation, located in coding exon 4 of the MSH2 gene, results from a duplication of A at nucleotide position 687, causing a translational frameshift with a predicted alternate stop codon (p.A230Sfs*2). This mutation has been reported in Japanese and Sicilian families meeting Amsterdam criteria (Miyaki M et al. J. Mol. Med. 1995 Oct;73:515-20; Cavallaro A et al. Int J Surg, 2014 Sep;12 Suppl 2:S120-S124). Of note, this alteration is also designated "truncation at codon 230-231" and "A insertion in the region surround the 227 and 228 codons of exon 4" in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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, |
RCV003452960 | SCV004188058 | 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. |
| Baylor Genetics | RCV003452960 | SCV004196860 | pathogenic | Lynch syndrome 1 | 2023-04-06 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001353749 | SCV000592477 | uncertain significance | not provided | no assertion criteria provided | clinical testing |