Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001226422 | SCV001398735 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-11-07 | 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: 954038). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1234Argfs*4) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). |
Ambry Genetics | RCV002348762 | SCV002621281 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-21 | criteria provided, single submitter | clinical testing | The c.3699dupA pathogenic mutation, located in coding exon 8 of the MSH6 gene, results from a duplication of A at nucleotide position 3699, causing a translational frameshift with a predicted alternate stop codon (p.E1234Rfs*4). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation. |