Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV001784680 | SCV002017578 | pathogenic | not provided | 2019-03-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002359254 | SCV002623162 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-07-30 | criteria provided, single submitter | clinical testing | The p.Q1328* pathogenic mutation (also known as c.3982C>T), located in coding exon 9 of the MSH6 gene, results from a C to T substitution at nucleotide position 3982. This changes the amino acid from a glutamine 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, |
RCV003451930 | SCV004185652 | 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. |
Color Diagnostics, |
RCV002359254 | SCV004357778 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-06 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 9 of the MSH6 gene, creating a premature translation stop signal. This variant is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. Although functional studies have not been reported, this variant is expected to disrupt the C-terminal MSH2 binding domain (PMID: 12019211). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. In addition, downstream truncations are known to be disease-causing (ClinVar variation ID: 42472, 525790, 218076). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as Pathogenic. |