Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000572454 | SCV000661740 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-04-26 | criteria provided, single submitter | clinical testing | The c.133delA pathogenic mutation, located in coding exon 1 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 133, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
Invitae | RCV001386761 | SCV001587109 | pathogenic | Familial cancer of breast | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr45Argfs*16) 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 (ExAC 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: 479558). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV001386761 | SCV004186654 | pathogenic | Familial cancer of breast | 2023-07-19 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |