Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022687 | SCV001184451 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-09 | criteria provided, single submitter | clinical testing | The p.H1518R variant (also known as c.4553A>G), located in coding exon 29 of the ATM gene, results from an A to G substitution at nucleotide position 4553. The histidine at codon 1518 is replaced by arginine, an amino acid with highly 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. |
| Fulgent Genetics, |
RCV002481830 | SCV002783098 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002550878 | SCV002932119 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1518 of the ATM protein (p.His1518Arg). This variant is not present in population databases (gnomAD 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: 824995). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |