Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000235731 | SCV000293053 | uncertain significance | not provided | 2024-12-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV000797726 | SCV000937304 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | 2022-11-17 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 245878). This variant has not been reported in the literature in individuals affected with DNM2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 425 of the DNM2 protein (p.Leu425Met). |
| Ambry Genetics | RCV002374392 | SCV002684834 | uncertain significance | Inborn genetic diseases | 2022-02-21 | criteria provided, single submitter | clinical testing | The p.L425M variant (also known as c.1273C>A), located in coding exon 10 of the DNM2 gene, results from a C to A substitution at nucleotide position 1273. The leucine at codon 425 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |