Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001044771 | SCV001208586 | pathogenic | Charcot-Marie-Tooth disease type 2E | 2019-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 440 of the NEFL protein (p.Pro440Leu). 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 (CMT) disease in a family (PMID: 25802885) and has been reported in unrelated individuals affected with CMT (PMID: 21149811, 30373780). ClinVar contains an entry for this variant (Variation ID: 155738). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic. |
Northcott Neuroscience Laboratory, |
RCV000143808 | SCV000188701 | probable-pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
Inherited Neuropathy Consortium | RCV000789071 | SCV000928420 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |