Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204463 | SCV000260870 | pathogenic | Charcot-Marie-Tooth disease, type 4A | 2019-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln163*) in the GDAP1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs104894077, ExAC 0.02%). This particular variant has been reported in many individuals affected with autosomal recessive Charcot-Marie-Tooth disease, and co-segregates with disease in several families (PMID: 11743580, 12601710, 20849849). ClinVar contains an entry for this variant (Variation ID: 4193). Loss-of-function variants in GDAP1 are known to be pathogenic (PMID: 11743580, 20685671). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000236485 | SCV000292799 | pathogenic | not provided | 2017-03-09 | criteria provided, single submitter | clinical testing | The Q163X nonsense variant in the GDAP1 gene has been reported previously in association with autosomal recessive Charcot-Marie-Tooth (CMT) disease and is hypothesized to be a founder mutation in the Spanish population (Boerkoel et al., 2003; Cuesta et al., 2002). Heterozygous carriers of the Q163X variant were reported to be unaffected (Boerkoel et al., 2003). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project and was not observed with any significant frequency in the 1000 Genomes Project. |
Fulgent Genetics, |
RCV000763605 | SCV000894451 | pathogenic | Charcot-Marie-Tooth disease type 2K; Charcot-Marie-Tooth disease, type 4A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive; Charcot-Marie-Tooth disease, recessive intermediate A | 2018-10-31 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004413 | SCV000024586 | pathogenic | Neuropathy, axonal, with vocal cord paresis, autosomal recessive | 2005-04-01 | no assertion criteria provided | literature only | |
Gene |
RCV000031963 | SCV000054655 | pathologic | Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive | 2012-09-13 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Genesis Genome Database | RCV000857207 | SCV000999789 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research | |
Inherited Neuropathy Consortium | RCV000857207 | SCV001190053 | likely pathogenic | Charcot-Marie-Tooth disease | no assertion criteria provided | provider interpretation |