Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519479 | SCV000617776 | pathogenic | not provided | 2017-07-14 | criteria provided, single submitter | clinical testing | The R310Q pathogenic variant in the GDAP1 gene has been previously reported with a pathogenic variant on the opposite allele (in trans) as a in two siblings with with autosomal recessive CMT (Azzedine et al., 2003). Functional studies demonstrate that R310Q induces peroxisomal fission and allows fusion of the mitochondrial matrix (Huber et al., 2013). The R310Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R310Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Therefore, R282C is interpreted to be a pathogenic variant. |
| Invitae | RCV001383587 | SCV001582780 | pathogenic | Charcot-Marie-Tooth disease type 4A | 2020-04-29 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect GDAP1 protein function (PMID: 21965300, 23628762, 19782751, 16172208, 19340293, 27841286). This variant has been observed in combination with another GDAP1 variant in individual(s) with autosomal recessive Charcot-Marie-Tooth disease (PMID: 12868504). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449535). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 310 of the GDAP1 protein (p.Arg310Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. |
| Mayo Clinic Laboratories, |
RCV000519479 | SCV001713473 | pathogenic | not provided | 2020-10-13 | criteria provided, single submitter | clinical testing | PS3, PM2, PM3, PM5, PP1, PP3 |
| Inherited Neuropathy Consortium | RCV000789782 | SCV000929166 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
| Inherited Neuropathy Consortium Ii, |
RCV003447143 | SCV004174602 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2K | 2016-01-06 | no assertion criteria provided | literature only |