Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159705 | SCV000209716 | uncertain significance | not provided | 2016-08-03 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.3085A>T at the cDNA level, p.Thr1029Ser (T1029S) at the protein level, and results in the change of a Threonine to a Serine (ACA>TCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Thr1029Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. ATM Thr1029Ser occurs at a position that is not conserved and is located in the region of interaction with beta-adaptin (Tavtigian 2009). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether ATM Thr1029Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Labcorp Genetics |
RCV000234598 | SCV000282920 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1029 of the ATM protein (p.Thr1029Ser). 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: 181938). 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. |
Color Diagnostics, |
RCV001180649 | SCV001345637 | likely benign | Hereditary cancer-predisposing syndrome | 2016-11-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001180649 | SCV002608838 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | The p.T1029S variant (also known as c.3085A>T), located in coding exon 20 of the ATM gene, results from an A to T substitution at nucleotide position 3085. The threonine at codon 1029 is replaced by serine, an amino acid with similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV004567191 | SCV005057156 | uncertain significance | Familial cancer of breast | 2023-12-12 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000234598 | SCV002079732 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-12-04 | no assertion criteria provided | clinical testing |