Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001190881 | SCV001358512 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 59 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 | RCV001389297 | SCV001590607 | pathogenic | Ataxia-telangiectasia syndrome | 2023-09-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln2874*) 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 clinical features of ATM-related conditions (PMID: 12815592, 28580595). ClinVar contains an entry for this variant (Variation ID: 927542). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001389297 | SCV004099829 | pathogenic | Ataxia-telangiectasia syndrome | 2023-09-14 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.8620C>T (p.Gln2874X) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250348 control chromosomes (gnomAD). c.8620C>T has been reported in the literature in at-least one individual affected with Ataxia-Telangiectasia (example: Coutinho_2004). The following publication has been ascertained in the context of this evaluation (PMID: 15039971). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |