Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491319 | SCV000580317 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-04-07 | criteria provided, single submitter | clinical testing | The p.E484* pathogenic mutation (also known as c.1450G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 1450. This changes the amino acid from a glutamic acid 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. |
| Color Diagnostics, |
RCV000491319 | SCV001345490 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-11-04 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 4 of the MSH6 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. 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. Based on the available evidence, this variant is classified as Pathogenic. |
| Labcorp Genetics |
RCV001865528 | SCV002231876 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-08-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428403). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu484*) 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). |
| Myriad Genetics, |
RCV003449325 | SCV004185757 | pathogenic | Lynch syndrome 5 | 2023-08-14 | 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. |
| Baylor Genetics | RCV003464058 | SCV004195729 | likely pathogenic | Endometrial carcinoma | 2023-11-11 | criteria provided, single submitter | clinical testing |