ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.68C>G (p.Thr23Arg) (rs906563423)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471834 SCV000552820 likely pathogenic Charcot-Marie-Tooth disease, type I 2017-07-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 23 of the PMP22 protein (p.Thr23Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth disease, type 1A (CMT1A) and has been observed to segregate with CMT1A in a single family (PMID: 23263778, 15099592, Invitae). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.
Athena Diagnostics Inc RCV000518509 SCV000614680 uncertain significance not specified 2017-03-08 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789510 SCV000928866 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Clinical Genetics,Academic Medical Center RCV001701010 SCV001925168 pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV001701010 SCV001956011 likely pathogenic not provided no assertion criteria provided clinical testing

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