Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076311 | SCV000107332 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV000570107 | SCV000669859 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-22 | criteria provided, single submitter | clinical testing | The c.187dupG pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a duplication of G at nucleotide position 187, causing a translational frameshift with a predicted alternate stop codon (p.V63Gfs*19). This mutation, designated as "G5>G6 frameshift at 183-187," was identified in a Taiwanese HNPCC family meeting Amsterdam II criteria (Huang RL et al. Cancer Genet. Cytogenet. 2004 Sep;153:108-14). 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, |
RCV003452866 | SCV004187926 | pathogenic | Lynch syndrome 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Invitae | RCV003593897 | SCV004292473 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-06-20 | 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: 90809). This variant is also known as G5 to G6 frame-shift at 183–187. This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 11393127, 31615790). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val63Glyfs*19) 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). |