Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Kariminejad - |
RCV001007469 | SCV001167084 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001007469 | SCV001230660 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | 2024-01-08 | 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 290 of the DNM2 protein (p.Arg290Gln). This variant is present in population databases (rs117398902, gnomAD 0.006%). This missense change has been observed in individuals with Charcot-Marie-Tooth disease and/or congenital myopathy (PMID: 32657593, 33333461). ClinVar contains an entry for this variant (Variation ID: 816534). 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. |
Ambry Genetics | RCV002372730 | SCV002685223 | uncertain significance | Inborn genetic diseases | 2021-04-08 | criteria provided, single submitter | clinical testing | The p.R290Q variant (also known as c.869G>A), located in coding exon 7 of the DNM2 gene, results from a G to A substitution at nucleotide position 869. The arginine at codon 290 is replaced by glutamine, an amino acid with highly similar properties. This variant was detected in an individual with congenital myopathy (Natera-de Benito D et al. Pediatr Neurol, 2021 Feb;115:50-65). 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. |
Gene |
RCV003106093 | SCV003761766 | uncertain significance | not provided | 2022-07-28 | criteria provided, single submitter | clinical testing | Identified in a patient with congenital myopathy, but it is unknown whether this individual was tested for variants in other genes associated with congenital myopathy (Natera-de Benito et al., 2021); Reported in a patient with hereditary neuropathy; however, familial segregation information was not included (Taghizadeh et al., 2020); 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 (HGMD); This variant is associated with the following publications: (PMID: 16227997, 33333461, 32657593) |