ClinVar Miner

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

dbSNP: rs906563423
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000471834 SCV000552820 pathogenic Charcot-Marie-Tooth disease, type I 2024-02-23 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 23 of the PMP22 protein (p.Thr23Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease, type 1A (CMT1A) (PMID: 15099592, 23263778; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 411592). 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 expected to disrupt PMP22 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV001701010 SCV000614680 likely pathogenic not provided 2017-10-12 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. This variant appears to segregate with disease in at least one family, however, the available information does not rule out segregation due to chance.
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
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001701010 SCV001956011 likely pathogenic not provided no assertion criteria provided clinical testing

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