Submissions for variant NM_000530.8(MPZ):c.190_192del (p.Phe64del)

dbSNP: rs1571819975

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Concord Molecular Medicine Laboratory, Concord Repatriation General Hospital	RCV003230591	SCV003928001	likely pathogenic	Charcot-Marie-Tooth disease type 1B	2023-01-17	criteria provided, single submitter	clinical testing	A heterozygous in-frame deletion resulting in the deletion of a phenylalanine residue at position 64 in the MPZ protein has been detected in a patient with a clinical diagnosis of Charcot-Marie-Tooth type 1. Patient has ankle dorsiflexion weakness with absent reflexes, and scoliosis. Nerve conduction study was consistent with CMT. The variant also segregates with disease with one affected family member. This variant has been previously reported in homozygous and heterozygous state in one family affected by CMT in literature (PMID: 8630052). The variant is located in a mutational hotspot and a critical functional domain (Immunoglobulin V-set domain, PF07686). The variant is absent in population database (gnomAD). A different in-frame deletion of an adjacent amino acid, serine at position 63, has also been described to cause CMT (PMID: 22734905). The current evidence allows a classification of this variant as likely pathogenic (ACMG criteria: PM4, PM1, PS4_supporting, PM2_supporting).
Inherited Neuropathy Consortium	RCV000789445	SCV000928801	uncertain significance	Dejerine-Sottas disease		no assertion criteria provided	literature only