Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697077 | SCV000825667 | uncertain significance | Charcot-Marie-Tooth disease, type 4A | 2018-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 282 of the GDAP1 protein (p.Arg282His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs375431837, ExAC 0.01%). This variant has been observed in combination with another GDAP1 variant in individuals affected with Charcot-Marie-Tooth disease (PMID: PMID:21326314, 22206013). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Inherited Neuropathy Consortium | RCV000789687 | SCV000929062 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |