Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001825149 | SCV002074531 | likely pathogenic | Ataxia-telangiectasia syndrome | 2022-01-05 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.4358delT (p.Ile1453LysfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and in the HGMD database with an associated phenotype of Ataxia Telangiectasia and/or cancers. The variant was absent in 251162 control chromosomes (gnomAD). To our knowledge, c.4358delT has not been reported in in individuals affected with Ataxia Telangiectasia, but has been reported in at least one individual affected with breast cancer (example, Palmer_2020) and in the isolated tumor tissue from a patient affected with head and neck squamous cell cancer (example, Ma-2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic for Ataxia Telangiectasia and associated cancer susceptibility. |
| Myriad Genetics, |
RCV004041009 | SCV004930622 | pathogenic | Familial cancer of breast | 2024-01-24 | 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 | RCV004041010 | SCV005016925 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | The c.4358delT pathogenic mutation, located in coding exon 28 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 4358, causing a translational frameshift with a predicted alternate stop codon (p.I1453Kfs*5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |