Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000490994 | SCV000580259 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-12 | criteria provided, single submitter | clinical testing | The c.1458_1459delTG pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1458 to 1459, causing a translational frameshift with a predicted alternate stop codon (p.E487Dfs*10). This mutation has been reported in a patient with microsatellite stable colon cancer (Latham A et al. J Clin Oncol, 2019 02;37:286-295). In addition to the clinical data presented in the literature, 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. |
Labcorp Genetics |
RCV001856942 | SCV002157490 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu487Aspfs*10) 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 present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 428371). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003449315 | SCV004188325 | pathogenic | Lynch syndrome 5 | 2023-08-14 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Baylor Genetics | RCV003464054 | SCV004197567 | pathogenic | Endometrial carcinoma | 2023-10-29 | criteria provided, single submitter | clinical testing |