Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234459 | SCV001407108 | uncertain significance | Charcot-Marie-Tooth disease, type 4A | 2019-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with alanine at codon 219 of the GDAP1 protein (p.Val219Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GDAP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Val219 amino acid residue in GDAP1. Other variant(s) that disrupt this residue have been observed in individuals with GDAP1-related conditions (PMID: 19500985, 21692914), which suggests that this may be a clinically significant amino acid residue. 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. |