Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221079 | SCV000273374 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-06 | criteria provided, single submitter | clinical testing | The p.V455M variant (also known as c.1363G>A), located in coding exon 9 of the ATM gene, results from a G to A substitution at nucleotide position 1363. The valine at codon 455 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Color Diagnostics, |
RCV000221079 | SCV000687304 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 455 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 ATM-related disorders in the literature. This variant has been identified in 3/251402 chromosomes 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 |
RCV000801607 | SCV000941391 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 455 of the ATM protein (p.Val455Met). This variant is present in population databases (rs368879876, gnomAD 0.006%). 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: 229981). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. 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. |
| Neuberg Centre For Genomic Medicine, |
RCV003338464 | SCV004047790 | uncertain significance | Familial cancer of breast | criteria provided, single submitter | clinical testing | The missense variant c.1363G>A (p.Val455Met) in ATM has been submitted to ClinVar as a Variant of Uncertain Significance (VUS). The p.Val455Met variant has allele frequency of 0.0012% in the gnomAD and novel (not in any individuals) in 1000 genome database. The amino acid Val at position 455 is changed to a Met changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Val455Met in ATM is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS). | |
| Baylor Genetics | RCV003338464 | SCV004210196 | uncertain significance | Familial cancer of breast | 2023-07-05 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000801607 | SCV002090990 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-10-15 | no assertion criteria provided | clinical testing |