Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686580 | SCV000814103 | pathogenic | Ataxia-telangiectasia syndrome | 2020-11-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu450Asnfs*23) in the ATM gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant has been observed in an individual affected with ataxia-telangiectasia (PMID: 12815592). ClinVar contains an entry for this variant (Variation ID: 566700). This variant is present in population databases (rs758004668, ExAC 0.009%). |
Ambry Genetics | RCV002386169 | SCV002689910 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-07 | criteria provided, single submitter | clinical testing | The c.1348delG pathogenic mutation, located in coding exon 9 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 1348, causing a translational frameshift with a predicted alternate stop codon (p.E450Nfs*23). This alteration was identified in an individual diagnosed with ataxia telangiectasia (Mitui M et al. Hum Mutat, 2003 Jul;22:43-50). Additionally, this alteration was identified in 0/3030 pancreatic cancer cases and 1/123136 population controls (Hu C et al. JAMA, 2018 06;319:2401-2409). 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 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, |
RCV004026238 | SCV004931059 | 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. |