Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001229826 | SCV001402283 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-10-31 | criteria provided, single submitter | clinical testing | 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 valine with alanine at codon 2774 of the ATM protein (p.Val2774Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. 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. |
| Ambry Genetics | RCV004032681 | SCV005020562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-31 | criteria provided, single submitter | clinical testing | The p.V2774A variant (also known as c.8321T>C), located in coding exon 56 of the ATM gene, results from a T to C substitution at nucleotide position 8321. The valine at codon 2774 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |