ClinVar Miner

Submissions for variant NM_018972.4(GDAP1):c.811G>A (p.Gly271Arg) (rs775622226)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000530141 SCV000644081 likely pathogenic Charcot-Marie-Tooth disease, type 4A 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 271 of the GDAP1 protein (p.Gly271Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs775622226, ExAC 0.02%). This variant has been observed in combination with another GDAP1 variant in individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 14561495, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Experimental studies have shown that this missense change alters mitochondrial dynamics when overexpressed in vitro (PMID: 23628762). 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV000789643 SCV001336402 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789643 SCV000929015 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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