Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011339 | SCV001171647 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | The c.1401dupA pathogenic mutation, located in coding exon 9 of the MSH2 gene, results from a duplication of A at nucleotide position 1401, causing a translational frameshift with a predicted alternate stop codon (p.F468Ifs*8). 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. |
Color Diagnostics, |
RCV001011339 | SCV001359277 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 9 of the MSH2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Invitae | RCV001862778 | SCV002142842 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe468Ilefs*8) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 819093). This variant is not present in population databases (ExAC no frequency). |