Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561169 | SCV000660612 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-01-23 | criteria provided, single submitter | clinical testing | The p.S1357Y variant (also known as c.4070C>A), located in coding exon 26 of the ATM gene, results from a C to A substitution at nucleotide position 4070. The serine at codon 1357 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
| Athena Diagnostics | RCV001288010 | SCV001474795 | uncertain significance | not provided | 2020-01-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003767091 | SCV004636357 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1357 of the ATM protein (p.Ser1357Tyr). This variant is not present in population databases (gnomAD no frequency). 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: 478986). 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 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. |