Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000467501 | SCV000546766 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 2638 of the ATM protein (p.Trp2638Cys). This variant is present in population databases (rs758843096, gnomAD 0.002%). 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: 407514). 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 expected to disrupt ATM protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV000569832 | SCV000668027 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-27 | criteria provided, single submitter | clinical testing | The c.7914G>T variant (also known as p.W2638C), located in coding exon 52 of the ATM gene, results from a G to T substitution at nucleotide position 7914. The tryptophan at codon 2638 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Natera, |
RCV000467501 | SCV002075987 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-18 | no assertion criteria provided | clinical testing |