Submissions for variant NM_018972.4(GDAP1):c.487C>T (p.Gln163Ter) (rs104894077)

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Total submissions: 5

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics,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
GeneDx	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.
GeneReviews	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.
Invitae	RCV000204463	SCV000260870	pathogenic	Charcot-Marie-Tooth disease, type 4A	2019-01-07	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 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.
OMIM	RCV000004413	SCV000024586	pathogenic	Neuropathy, axonal, with vocal cord paresis, autosomal recessive	2005-04-01	no assertion criteria provided	literature only

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