ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.670G>T (p.Asp224Tyr) (rs267607247)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000033921 SCV000057838 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-03-26 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789431 SCV000928786 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000700463 SCV000829220 pathogenic Charcot-Marie-Tooth disease, type I 2018-04-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 224 of the MPZ protein (p.Asp224Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a family segregating with disease (PMID: 19882637) and in multiple unrelated individuals affected with Charcot-Marie-Tooth disease (CMT) (PMID:21149811, 19259128, 27088055). This variant has also been reported as homozygous in a family with CMT type 1B (PMID:16488608). ClinVar contains an entry for this variant (Variation ID: 41024). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.

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