Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709195 | SCV000838620 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001018341 | SCV001179567 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-21 | criteria provided, single submitter | clinical testing | The p.C2930W variant (also known as c.8790C>G), located in coding exon 60 of the ATM gene, results from a C to G substitution at nucleotide position 8790. The cysteine at codon 2930 is replaced by tryptophan, an amino acid with highly 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. |
| Labcorp Genetics |
RCV000709195 | SCV002280743 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-11-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 584800). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 2930 of the ATM protein (p.Cys2930Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. |