Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000542442 | SCV000644076 | pathogenic | Charcot-Marie-Tooth disease type 4A | 2022-11-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GDAP1 protein in which other variant(s) (p.Phe263Leufs*22) have been determined to be pathogenic (PMID: 12499475). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 467768). This premature translational stop signal has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 28751717). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln235*) in the GDAP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 124 amino acid(s) of the GDAP1 protein. |