ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.458C>T (p.Pro153Leu) (rs538412810)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471926 SCV000544591 likely pathogenic Charcot-Marie-Tooth disease, type 4A 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 153 of the GDAP1 protein (p.Pro153Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs538412810, ExAC 0.009%). This variant has been observed in the homozygous state in several individuals affected with Charcot-Marie-Tooth disease (PMID: 18421898, 18504680, 28751717, 28244113, Invitae). ClinVar contains an entry for this variant (Variation ID: 406135). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CMT Laboratory,Bogazici University RCV000471926 SCV001548303 pathogenic Charcot-Marie-Tooth disease, type 4A 2020-12-01 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789054 SCV000928403 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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