Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001316286 | SCV001506895 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-07-29 | 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 isoleucine with phenylalanine at codon 1846 of the ATM protein (p.Ile1846Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine. |
| Ambry Genetics | RCV005271147 | SCV005943433 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-01-23 | criteria provided, single submitter | clinical testing | The p.I1846F variant (also known as c.5536A>T), located in coding exon 36 of the ATM gene, results from an A to T substitution at nucleotide position 5536. The isoleucine at codon 1846 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |