Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826178 | SCV000967717 | likely pathogenic | Lynch syndrome | 2017-12-14 | criteria provided, single submitter | clinical testing | The p.Arg1318X variant in MSH6 has not been previously reported in individuals w ith MSH6-associated cancers and was absent from large population studies. This n onsense variant leads to a premature termination codon at position 1318. This te rmination codon occurs within the terminal 50 bases of the second to last exon a nd is more likely to escape nonsense mediated decay (NMD), resulting in a trunca ted protein. Truncating variants downstream of this variant have been reported i n individuals with Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Arg1318X variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_Strong; PM2. |
| Ambry Genetics | RCV002352477 | SCV002621041 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-27 | criteria provided, single submitter | clinical testing | The p.R1318* pathogenic mutation (also known as c.3952A>T), located in coding exon 9 of the MSH6 gene, results from an A to T substitution at nucleotide position 3952. This changes the amino acid from an arginine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003453759 | SCV004188228 | pathogenic | Lynch syndrome 5 | 2023-08-28 | 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. |
| Labcorp Genetics |
RCV003594042 | SCV004320540 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2025-01-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1318*) 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). This premature translational stop signal has been observed in individual(s) with lymphoma (PMID: 33809641). ClinVar contains an entry for this variant (Variation ID: 667409). For these reasons, this variant has been classified as Pathogenic. |