Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010468 | SCV001170672 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.W411* pathogenic mutation (also known as c.1233G>A), located in coding exon 10 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1233. This changes the amino acid from a tryptophan to a stop codon within coding exon 10. 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. |
| Invitae | RCV001862769 | SCV002233071 | pathogenic | Familial cancer of breast | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp411*) 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 premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 29271107, 29785153, 31159747). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 818661). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV001862769 | SCV004043333 | pathogenic | Familial cancer of breast | 2023-06-28 | 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. |