Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055971 | SCV001220386 | pathogenic | Charcot-Marie-Tooth disease type 4A | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 327 of the GDAP1 protein (p.Gly327Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive Charcot-Marie-Tooth disease (PMID: 21365284, 32376792; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 40049). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GDAP1 function (PMID: 21365284, 33477664). For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV003152669 | SCV003841568 | likely pathogenic | Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 21365284). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.83; 3Cnet: 0.73). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with GDAP1-related disorder (ClinVar ID: VCV000040049 / PMID: 21365284). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| OMIM | RCV000033148 | SCV000056930 | pathogenic | Charcot-Marie-Tooth disease recessive intermediate A | 2011-05-01 | no assertion criteria provided | literature only | |
| Inherited Neuropathy Consortium Ii, |
RCV003447102 | SCV004174606 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2K | 2016-01-06 | no assertion criteria provided | literature only |