Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000255142 | SCV000322690 | likely pathogenic | not provided | 2016-08-19 | criteria provided, single submitter | clinical testing | This variant is denoted CHEK2 c.902T>A at the cDNA level and p.Leu301Ter (L301X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTG>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, it is considered likely pathogenic. |
| Invitae | RCV000545100 | SCV000633228 | pathogenic | Familial cancer of breast | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu301*) in the CHEK2 gene. RNA analysis indicates that this premature translational stop signal induces altered splicing and may result in an absent or disrupted protein product. 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: 265694). Studies have shown that this premature translational stop signal results in skipping of exon 8 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000573767 | SCV000661760 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-03-25 | criteria provided, single submitter | clinical testing | The p.L301* pathogenic mutation (also known as c.902T>A), located in coding exon 7 of the CHEK2 gene, results from a T to A substitution at nucleotide position 902. This changes the amino acid from a leucine to a stop codon within coding exon 7. 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. |
| Counsyl | RCV000545100 | SCV000677843 | likely pathogenic | Familial cancer of breast | 2017-01-12 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV000545100 | SCV004020157 | 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 | RCV000545100 | SCV004217520 | likely pathogenic | Familial cancer of breast | 2023-10-06 | criteria provided, single submitter | clinical testing |