Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001038861 | SCV001202360 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 718 of the DNM2 protein (p.Arg718Gln). This variant is present in population databases (rs753677038, gnomAD 0.01%). This missense change has been observed in individual(s) with centronuclear myopathy (PMID: 25501959). ClinVar contains an entry for this variant (Variation ID: 837508). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNM2 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. |
| Gene |
RCV001759734 | SCV001987693 | uncertain significance | not provided | 2020-08-26 | criteria provided, single submitter | clinical testing | Reported in a patient with centronuclear myopathy; this patient also had a pathogenic variant in the DNM2 gene identified (Chen et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 25501959) |
| Ambry Genetics | RCV002427493 | SCV002731247 | uncertain significance | Inborn genetic diseases | 2021-06-22 | criteria provided, single submitter | clinical testing | The p.R718Q variant (also known as c.2153G>A), located in coding exon 19 of the DNM2 gene, results from a G to A substitution at nucleotide position 2153. The arginine at codon 718 is replaced by glutamine, an amino acid with highly similar properties. This variant was detected in an individual with centronuclear myopathy, who also had a known pathogenic variant in DNM2 (Chen T et al. Neurol Sci, 2015 May;36:735-41). 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. |