Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001239078 | SCV001411924 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-04-05 | 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. 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 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 histidine with tyrosine at codon 2480 of the ATM protein (p.His2480Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Ambry Genetics | RCV002379912 | SCV002670291 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-25 | criteria provided, single submitter | clinical testing | The p.H2480Y variant (also known as c.7438C>T), located in coding exon 49 of the ATM gene, results from a C to T substitution at nucleotide position 7438. The histidine at codon 2480 is replaced by tyrosine, an amino acid with 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. |