Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002029635 | SCV002304262 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-06-22 | 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 with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 2434 of the ATM protein (p.Thr2434Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Ambry Genetics | RCV002386917 | SCV002669710 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-30 | criteria provided, single submitter | clinical testing | The p.T2434I variant (also known as c.7301C>T), located in coding exon 48 of the ATM gene, results from a C to T substitution at nucleotide position 7301. The threonine at codon 2434 is replaced by isoleucine, an amino acid with similar properties. 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 this alteration remains unclear. |