Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701665 | SCV000830477 | pathogenic | Ataxia-telangiectasia syndrome | 2022-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg457Thrfs*30) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 578602). 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). |
Myriad Genetics, |
RCV004026567 | SCV004931866 | pathogenic | Familial cancer of breast | 2024-01-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Ambry Genetics | RCV004026568 | SCV005036132 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | The c.1368dupA pathogenic mutation, located in coding exon 9 of the ATM gene, results from a duplication of A at nucleotide position 1368, causing a translational frameshift with a predicted alternate stop codon (p.R457Tfs*30). Amongst two different cohort studies, this variant was identified in 0 of 13087 breast cancer cases and at least 1 of 5488 control individuals in the UK, and in 1 of 535 pancreatic ductal adenocarcinoma cases (Decker B et al. J Med Genet, 2017 Nov;54:732-741; Zimmermann MT et al. Front Oncol, 2021 Mar;11:606820). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this variant is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this variant is interpreted as a disease-causing mutation. |