ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.347T>G (p.Met116Arg) (rs281865060)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000031962 SCV000644067 pathogenic Charcot-Marie-Tooth disease, type 4A 2018-07-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with arginine at codon 116 of the GDAP1 protein (p.Met116Arg). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is present in population databases (rs281865060, ExAC 0.006%). This variant has been reported as homozygous or in combination with another GDAP1 variant in several individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 15377708, 25429913). This variant has been reported to segregate with Charcot-Marie-Tooth disease in a single family (PMID: 15377708). ClinVar contains an entry for this variant (Variation ID: 38411). Experimental studies have shown that this missense change is able to protect against oxidative glutamate toxicity to a lesser degree compared to wild-type (PMID: 21965300). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001092877 SCV001249596 pathogenic not provided 2020-12-01 criteria provided, single submitter clinical testing
GeneReviews RCV000031962 SCV000054653 pathologic Charcot-Marie-Tooth disease, type 4A 2012-09-13 no assertion criteria provided curation Converted during submission to Pathogenic.
Inherited Neuropathy Consortium RCV000789791 SCV000929175 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
GeneReviews RCV000789791 SCV001750193 pathogenic Charcot-Marie-Tooth disease 2017-03-30 no assertion criteria provided literature only

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