ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.47T>C (p.Leu16Pro) (rs104894617)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000685070 SCV000812542 pathogenic Charcot-Marie-Tooth disease, type I 2018-03-06 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 16 of the PMP22 protein (p.Leu16Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Charcot-Marie-Tooth disease, type 1 (CMT1) (PMID: 8995589) and has been reported to segregate with CMT1 in affected families (PMID: 8995589, 1303281). It has also been reported in an unrelated individual affected with CMT1 (PMID: 23689413). ClinVar contains an entry for this variant (Variation ID: 8428). Experimental studies have shown that this missense change results in an unstable, improperly folded and mislocalized protein (PMID: 26102530, 18795802, 21827951, 25385046, 9425015). Furthermore, mouse models with this missense change recapitulate the human phenotype (PMID: 6313869, 12090404). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008940 SCV000029150 pathogenic Charcot-Marie-Tooth disease, type IA 1993-05-01 no assertion criteria provided literature only
GeneReviews RCV000008940 SCV000055666 pathologic Charcot-Marie-Tooth disease, type IA 2012-10-18 no assertion criteria provided curation Converted during submission to Pathogenic.

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