Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000031962 | SCV000644067 | pathogenic | Charcot-Marie-Tooth disease, type 4A | 2018-07-09 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with arginine at codon 116 of the GDAP1 protein (p.Met116Arg). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is present in population databases (rs281865060, ExAC 0.006%). This variant has been reported as homozygous or in combination with another GDAP1 variant in several individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 15377708, 25429913). This variant has been reported to segregate with Charcot-Marie-Tooth disease in a single family (PMID: 15377708). ClinVar contains an entry for this variant (Variation ID: 38411). Experimental studies have shown that this missense change is able to protect against oxidative glutamate toxicity to a lesser degree compared to wild-type (PMID: 21965300). 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. |
Ce |
RCV001092877 | SCV001249596 | pathogenic | not provided | 2017-12-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000031962 | SCV000054653 | pathologic | Charcot-Marie-Tooth disease, type 4A | 2012-09-13 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Inherited Neuropathy Consortium | RCV000789791 | SCV000929175 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |