Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000527122 | SCV000644075 | likely pathogenic | Charcot-Marie-Tooth disease type 4A | 2022-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 218 of the GDAP1 protein (p.Gln218Arg). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gln218 amino acid residue in GDAP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18231710, 23628762, 26525999). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 GDAP1 protein function. ClinVar contains an entry for this variant (Variation ID: 467767). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 34169998; Invitae). This variant is not present in population databases (gnomAD no frequency). |