Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076656 | SCV000107691 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV001025203 | SCV001187345 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-08-30 | criteria provided, single submitter | clinical testing | The c.638_639delTG pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 638 to 639, causing a translational frameshift with a predicted alternate stop codon (p.L213Qfs*18). This mutation was reported in an individual diagnosed with MSI-H, MSH2/MSH6-absent colorectal cancer at age 42 (Rahner N et al. Acta Oncol. 2007;46(6):763-9). 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 | RCV003593903 | SCV004292476 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu213Glnfs*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). 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: 15849733). ClinVar contains an entry for this variant (Variation ID: 91152). For these reasons, this variant has been classified as Pathogenic. |