ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.458C>T (p.Pro153Leu)

gnomAD frequency: 0.00001  dbSNP: rs538412810
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000471926 SCV000544591 pathogenic Charcot-Marie-Tooth disease type 4A 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 153 of the GDAP1 protein (p.Pro153Leu). This variant is present in population databases (rs538412810, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive Charcot-Marie-Tooth disease (PMID: 18421898, 18504680, 28244113, 28751717; Invitae). ClinVar contains an entry for this variant (Variation ID: 406135). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GDAP1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Kariminejad - Najmabadi Pathology & Genetics Center RCV001836822 SCV001167077 likely pathogenic Peripheral neuropathy 2021-07-10 criteria provided, single submitter clinical testing
CMT Laboratory, Bogazici University RCV000471926 SCV001548303 pathogenic Charcot-Marie-Tooth disease type 4A 2020-12-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002506106 SCV002809057 likely pathogenic Charcot-Marie-Tooth disease axonal 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 2021-09-30 criteria provided, single submitter clinical testing
GeneDx RCV004719824 SCV005324945 likely pathogenic not provided 2023-11-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33477664, 28244113, 31673878, 28220846, 21892769, 18504680, 18421898, 28751717, 32657593)
Inherited Neuropathy Consortium RCV000789054 SCV000928403 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV003447135 SCV004174600 uncertain significance Charcot-Marie-Tooth disease axonal type 2K 2016-01-06 no assertion criteria provided literature only

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