ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.293G>C (p.Arg98Pro) (rs121913589)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000015237 SCV000255801 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2014-09-12 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000790115 SCV000929505 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000638160 SCV000759646 pathogenic Charcot-Marie-Tooth disease, type I 2018-02-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 98 of the MPZ protein (p.Arg98Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease type 1 (PMID: 8644725). ClinVar contains an entry for this variant (Variation ID: 14174). 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. A different missense substitution at this codon (p.Arg98His) has been determined to be pathogenic (PMID: 8644725, 20461396, 10581375, 20215982). This suggests that the arginine residue is critical for MPZ protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000015237 SCV000035496 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 1996-03-01 no assertion criteria provided literature only

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