Submissions for variant NM_000530.8(MPZ):c.314C>T (p.Pro105Leu) (rs786204215)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000168337	SCV000219026	pathogenic	Charcot-Marie-Tooth disease, type I	2019-08-14	criteria provided, single submitter	clinical testing	This sequence change replaces proline with leucine at codon 105 of the MPZ protein (p.Pro105Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with autosomal dominant Charcot-Marie-Tooth disease type-2 (CMT2) in families (PMID: 29465609, Invitae). ClinVar contains an entry for this variant (Variation ID: 188325). 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 and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173695	SCV001336806	likely pathogenic	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing

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