ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.769C>T (p.Arg257Ter) (rs770501034)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235362 SCV000292560 pathogenic not provided 2016-04-12 criteria provided, single submitter clinical testing The R257X nonsense mutation in the GDAP1 gene has been reported previously in association with CMT4A (Stenson et al.,2014 ). This mutation is predicted to cause loss of normal protein function through protein truncation as the last 102 amino acids of the protein are lost. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore the R257X mutation is interpreted to be a pathogenic mutation
CeGaT Praxis fuer Humangenetik Tuebingen RCV000235362 SCV001249599 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing
Invitae RCV001206561 SCV001377874 pathogenic Charcot-Marie-Tooth disease, type 4A 2019-08-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GDAP1 gene (p.Arg257*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 102 amino acids of the GDAP1 protein. This variant is present in population databases (rs770501034, ExAC 0.01%). This variant has been observed in combination with another GDAP1 variant in individuals affected with hereditary sensory and motor neuropathy (PMID: 21322820). ClinVar contains an entry for this variant (Variation ID: 245608). This variant disrupts the C-terminus of the GDAP1 protein. Other variant(s) that disrupt this region (p.Phe263Leufs*22, p.Arg341Glnfs*12) have been determined to be pathogenic (PMID: 12499475, 25614874, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics,Cologne University RCV000664207 SCV000787765 pathogenic Charcot-Marie-Tooth disease, recessive intermediate A 2018-04-25 no assertion criteria provided clinical testing
Inherited Neuropathy Consortium RCV000789164 SCV000928516 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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