Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076369 | SCV000107396 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV000491368 | SCV000580483 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-11 | criteria provided, single submitter | clinical testing | The c.2046_2047delTG pathogenic mutation, located in coding exon 13 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 2046 to 2047, causing a translational frameshift with a predicted alternate stop codon (p.V684Dfs*14). This pathogenic mutation is reported in the literature in a family meeting Amsterdam and/or Bethesda criteria (Dominguez-Valentin M et al. Hered Cancer Clin Pract 2013; 11(1):18). 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. |
Invitae | RCV001854324 | SCV002238354 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-07-20 | 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: 90867). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 24344984). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val684Aspfs*14) 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). |