Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055622 | SCV001220022 | likely pathogenic | Charcot-Marie-Tooth disease type 4A | 2021-04-09 | criteria provided, single submitter | clinical testing | 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. 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. This variant has been observed in individual(s) with neuropathy (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 851263). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 65 of the GDAP1 protein (p.Glu65Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
| 3billion | RCV001055622 | SCV002058604 | uncertain significance | Charcot-Marie-Tooth disease type 4A | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |