Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
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. |
Gene |
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 |