Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000217643 | SCV000279607 | pathogenic | not provided | 2015-11-24 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted MSH6 c.599C>G at the cDNA level and p.Ser200Ter (S200X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with colorectal cancer (Jenkins 2006). We therefore consider this variant to be pathogenic. |
| Ambry Genetics | RCV000491993 | SCV000580327 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-25 | criteria provided, single submitter | clinical testing | The p.S200* pathogenic mutation (also known as c.599C>G), located in coding exon 3 of the MSH6 gene, results from a C to G substitution at nucleotide position 599. This changes the amino acid from a serine to a stop codon within coding exon 3. 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 |
RCV000692262 | SCV000820076 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-09-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser200*) 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 colorectal cancer (PMID: 16616355). ClinVar contains an entry for this variant (Variation ID: 234621). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003454671 | SCV004188245 | pathogenic | Lynch syndrome 5 | 2023-08-10 | 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 | RCV003463614 | SCV004198171 | pathogenic | Endometrial carcinoma | 2022-02-22 | criteria provided, single submitter | clinical testing |