Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204789 | SCV000259390 | pathogenic | Lynch syndrome | 2015-07-12 | criteria provided, single submitter | clinical testing | This sequence change deletes 2 nucleotides in exon 12 of the MSH2 mRNA (c.1963_1964delGT), causing a frameshift at codon 655. This creates a premature translational stop signal (p.Val655Ilefs*3) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001388238 | SCV001589147 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val655Ilefs*3) 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 variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 219499). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003454538 | SCV004186885 | pathogenic | Lynch syndrome 1 | 2023-08-04 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |