Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575921 | SCV000660643 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-12 | criteria provided, single submitter | clinical testing | The p.Y1529* pathogenic mutation (also known as c.4587T>G), located in coding exon 29 of the ATM gene, results from a T to G substitution at nucleotide position 4587. This changes the amino acid from a tyrosine to a stop codon within coding exon 29. This alteration has been previously reported in a compound heterozygous (with c.538C>T) individual with ataxia telangiectasia (Heinrich T et al. Eur. J. Pediatr., 2006 Apr;165:250-7). 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. |
| Color Diagnostics, |
RCV000575921 | SCV000687561 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 30 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Invitae | RCV000627912 | SCV000748796 | pathogenic | Ataxia-telangiectasia syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr1529*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia telangiectasia (PMID: 16411093). ClinVar contains an entry for this variant (Variation ID: 479008). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Mendelics | RCV000627912 | SCV000838543 | pathogenic | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV002289774 | SCV002581713 | pathogenic | Familial cancer of breast | 2022-08-03 | criteria provided, single submitter | clinical testing |