Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575933 | SCV000665678 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-29 | criteria provided, single submitter | clinical testing | The p.H2125Y variant (also known as c.6373C>T), located in coding exon 43 of the ATM gene, results from a C to T substitution at nucleotide position 6373. The histidine at codon 2125 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000688020 | SCV000815616 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 2125 of the ATM protein (p.His2125Tyr). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 481348). 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 disruptive. 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. |
| Natera, |
RCV000688020 | SCV002083495 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-08-12 | no assertion criteria provided | clinical testing |