Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012176 | SCV001172599 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-23 | criteria provided, single submitter | clinical testing | The p.F523S variant (also known as c.1568T>C), located in coding exon 9 of the ATM gene, results from a T to C substitution at nucleotide position 1568. The phenylalanine at codon 523 is replaced by serine, an amino acid with highly dissimilar properties. This variant was reported in 0/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is not well 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. |
| Invitae | RCV001211187 | SCV001382713 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with serine at codon 523 of the ATM protein (p.Phe523Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine 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 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. |