Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001202537 | SCV001373650 | uncertain significance | Charcot-Marie-Tooth disease X-linked dominant 6 | 2023-02-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 231 of the PDK3 protein (p.Pro231Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with PDK3-related conditions. ClinVar contains an entry for this variant (Variation ID: 934194). 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 PDK3 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. |