Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000205564 | SCV000259424 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1312 of the ATM protein (p.Arg1312Gly). 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. 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. ClinVar contains an entry for this variant (Variation ID: 219517). This missense change has been observed in individual(s) with melanoma (PMID: 32325837). This variant is not present in population databases (gnomAD no frequency). |
| Mendelics | RCV000205564 | SCV000838529 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001021469 | SCV001183089 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-25 | criteria provided, single submitter | clinical testing | The p.R1312G variant (also known as c.3934A>G), located in coding exon 25 of the ATM gene, results from an A to G substitution at nucleotide position 3934. The arginine at codon 1312 is replaced by glycine, an amino acid with dissimilar properties. This variant was identified in 1/167 Italian individuals with cutaneous melanoma who were CDKN2A/ARF- and CDK4-negative (Pastorino L et al. Cancers (Basel), 2020 04;12:). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |