Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565349 | SCV000665559 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-29 | criteria provided, single submitter | clinical testing | The p.H2038Q variant (also known as c.6114C>A), located in coding exon 41 of the ATM gene, results from a C to A substitution at nucleotide position 6114. The histidine at codon 2038 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002526815 | SCV003298728 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with glutamine at codon 2038 of the ATM protein (p.His2038Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 481266). 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. 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. |