Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026756 | SCV001189196 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-29 | criteria provided, single submitter | clinical testing | The p.P2575Q variant (also known as c.7724C>A), located in coding exon 51 of the ATM gene, results from a C to A substitution at nucleotide position 7724. The proline at codon 2575 is replaced by glutamine, an amino acid with similar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV001345556 | SCV001539679 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-10-15 | 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. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 827222). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with glutamine at codon 2575 of the ATM protein (p.Pro2575Gln). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and glutamine. |