Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000200187 | SCV000253744 | pathogenic | Ataxia-telangiectasia syndrome | 2023-06-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 216023). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln2414*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). |
Ambry Genetics | RCV000492913 | SCV000581475 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-11 | criteria provided, single submitter | clinical testing | The p.Q2414* pathogenic mutation (also known as c.7240C>T), located in coding exon 48 of the ATM gene, results from a C to T substitution at nucleotide position 7240. This changes the amino acid from a glutamine to a stop codon within coding exon 48. This alteration has been detected in conjunction with a ATM pathogenic variant in an individual diagnosed with ataxia-telangiectasia (A-T) (Suspitsin E et al. Eur J Med Genet, 2020 Jan;63:103630). This alteration has also been reported in individuals diagnosed with pancreatic ductal adenocarcinomas (Brand R et al. Cancer, 2018 Sep;124:3520-3527). 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, |
RCV004020459 | SCV004932338 | pathogenic | Familial cancer of breast | 2024-01-31 | 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. |