Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000805833 | SCV000945805 | pathogenic | Familial cancer of breast | 2023-05-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp452*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 650644). A different variant (c.1356G>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 26681312, 28724667, 29356917). This suggests that this variant is also likely to be causative of disease. |
Ambry Genetics | RCV002381773 | SCV002693137 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-25 | criteria provided, single submitter | clinical testing | The p.W452* pathogenic mutation (also known as c.1355G>A), located in coding exon 11 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1355. This changes the amino acid from a tryptophan to a stop codon within coding exon 11. 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. |
Myriad Genetics, |
RCV000805833 | SCV004043909 | 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. |