Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001060634 | SCV001225338 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-08-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This sequence change creates a premature translational stop signal (p.Asp253Phefs*2) 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). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 855376). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002393295 | SCV002672950 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-13 | criteria provided, single submitter | clinical testing | The c.757_758delGA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 757 to 758, causing a translational frameshift with a predicted alternate stop codon (p.D253Ffs*2). 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, |
RCV003455274 | SCV004187253 | pathogenic | Lynch syndrome 5 | 2023-08-10 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |