Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000206762 | SCV000261594 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1296 of the ATM protein (p.Pro1296Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ataxia-telangiectasia (PMID: 21833744). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 220775). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV000478981 | SCV000568020 | uncertain significance | not provided | 2022-12-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25115387, 25589618, 26718692, 21833744) |
| Ambry Genetics | RCV000573505 | SCV000668148 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-17 | criteria provided, single submitter | clinical testing | The p.P1296S variant (also known as c.3886C>T), located in coding exon 25 of the ATM gene, results from a C to T substitution at nucleotide position 3886. The proline at codon 1296 is replaced by serine, an amino acid with similar properties. This alteration has been reported in an individual diagnosed with ataxia-telangiectasia (A-T) in conjunction with a pathogenic ATM mutation (Soukupova J et al. Neuromolecular Med. 2011 Sep;13:204-11). This variant has also been confirmed in trans with an ATM likely pathogenic variant in a second individual with clinical features of A-T (academic collaborator personal communication). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Color Diagnostics, |
RCV000573505 | SCV000682168 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-08 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000206762 | SCV000788637 | uncertain significance | Ataxia-telangiectasia syndrome | 2017-05-02 | criteria provided, single submitter | clinical testing |