Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001923610 | SCV002194886 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-06-12 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 554 of the ATM protein (p.Thr554Pro). |
| Ambry Genetics | RCV002397918 | SCV002707528 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-10-17 | criteria provided, single submitter | clinical testing | The p.T554P variant (also known as c.1660A>C), located in coding exon 10 of the ATM gene, results from an A to C substitution at nucleotide position 1660. The threonine at codon 554 is replaced by proline, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 66000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.T554P remains unclear. |
| Baylor Genetics | RCV004571621 | SCV005055940 | uncertain significance | Familial cancer of breast | 2024-03-17 | criteria provided, single submitter | clinical testing |