Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000218911 | SCV000277083 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-10 | criteria provided, single submitter | clinical testing | The p.Q69* pathogenic mutation (also known as c.205C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 205. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Gene |
RCV000222824 | SCV000279769 | pathogenic | not provided | 2018-06-25 | criteria provided, single submitter | clinical testing | This variant is denoted CHEK2 c.205C>T at the cDNA level and p.Gln69Ter (Q69X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature as a germline variant, it is considered pathogenic. |
| Counsyl | RCV000663138 | SCV000786282 | likely pathogenic | Familial cancer of breast | 2018-04-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000663138 | SCV001201634 | pathogenic | Familial cancer of breast | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln69*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 232837). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV000663138 | SCV004020084 | pathogenic | Familial cancer of breast | 2023-03-08 | 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 | RCV000663138 | SCV004217609 | likely pathogenic | Familial cancer of breast | 2023-08-04 | criteria provided, single submitter | clinical testing |