Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000463958 | SCV000546960 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 1431 of the ATM protein (p.Asn1431Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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. 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. |
| Sema4, |
RCV002257709 | SCV002534623 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-02 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002257709 | SCV002626682 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-03 | criteria provided, single submitter | clinical testing | The p.N1431S variant (also known as c.4292A>G), located in coding exon 28 of the ATM gene, results from an A to G substitution at nucleotide position 4292. The asparagine at codon 1431 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |