Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483015 | SCV000567910 | uncertain significance | not provided | 2015-09-14 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.5036G>T at the cDNA level, p.Gly1679Val (G1679V) at the protein level, and results in the change of a Glycine to a Valine (GGT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Gly1679Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. ATM Gly1679Val occurs at a position that is conserved across species and is located within the ATM kinase domain (Stracker 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Gly1679Val is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Labcorp Genetics |
RCV000554656 | SCV000622560 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 1679 of the ATM protein (p.Gly1679Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. 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. |
Ambry Genetics | RCV002341134 | SCV002644372 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-16 | criteria provided, single submitter | clinical testing | The p.G1679V variant (also known as c.5036G>T), located in coding exon 33 of the ATM gene, results from a G to T substitution at nucleotide position 5036. The glycine at codon 1679 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000554656 | SCV002078395 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-01-29 | no assertion criteria provided | clinical testing |