Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001941526 | SCV002237227 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-06-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp365*) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. |
Ambry Genetics | RCV003170170 | SCV003867520 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-13 | criteria provided, single submitter | clinical testing | The p.W365* pathogenic mutation (also known as c.1095G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 1095. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. 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, |
RCV003453857 | SCV004185753 | pathogenic | Lynch syndrome 5 | 2023-08-11 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |