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 | 2016-05-16 | 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 variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. 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. Since supporting evidence is limited at this time, the clinical significance of this alteration 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. |