Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222608 | SCV000276964 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | The p.V3005A variant (also known as c.9014T>C), located in coding exon 62 of the ATM gene, results from a T to C substitution at nucleotide position 9014. The valine at codon 3005 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587373 | SCV000694390 | uncertain significance | not provided | 2016-09-09 | criteria provided, single submitter | clinical testing | Variant summary: The ATM c.9014T>C (p.Val3005Ala) variant located in the protein kinase-like domain causes a missense change involving a conserved nucleotide with 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a "damaging" outcome, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP), nor has it been to our knowledge reported in affected individuals via publications. One clinical diagnostic laboratory has cited the variant as "uncertain significance." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Color Diagnostics, |
RCV000222608 | SCV000904877 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with alanine at codon 3005 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001360171 | SCV001556075 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 3005 of the ATM protein (p.Val3005Ala). 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: 232752). 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 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. |