Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145909 | SCV000193046 | pathogenic | Centronuclear myopathy | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002515958 | SCV003442658 | pathogenic | Charcot-Marie-Tooth disease dominant intermediate B | 2022-02-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 621 of the DNM2 protein (p.Leu621Pro). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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 DNM2 protein function. ClinVar contains an entry for this variant (Variation ID: 158519). This missense change has been observed in individuals with congenital or centronuclear myopathy (PMID: 19932620, 22396310; Invitae). This variant is not present in population databases (gnomAD no frequency). |
Inherited Neuropathy Consortium Ii, |
RCV002515958 | SCV004174759 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | 2019-05-26 | no assertion criteria provided | literature only |