ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.106A>T (p.Arg36Trp) (rs864622732)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204639 SCV000262192 pathogenic Charcot-Marie-Tooth disease, type I 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 36 of the MPZ protein (p.Arg36Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with acute onset painful polyneuropathy in a single family (PMID: 16616847). This variant has also been reported in an individual affected with late onset neuropathy (PMID: 26310628). ClinVar contains an entry for this variant (Variation ID: 221065). Nerve conduction studies and electromyogram (NCS/EMG) have shown that this missense change (p.Arg36Trp) causes sensorimotor polyneuropathy with axon loss and demyelination (PMID: 16616847). A different missense substitution at this codon (p.Arg36Gly) is reported to be deleterious (PMID: 23279346). This indicates that the Arginine residue is important for MPZ protein function. In addition, the Arginine residue resides in the extracellular domain of the MPZ protein and a significant number of previously reported MPZ pathogenic variants have been found within this domain (PMID: 14711881) For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000517562 SCV000614098 pathogenic not provided 2018-06-07 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789432 SCV000928787 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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