Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694043 | SCV000822469 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2021-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 135 of the MFN2 protein (p.Arg135Gln). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MFN2 protein function. ClinVar contains an entry for this variant (Variation ID: 549683). This missense change has been observed in individual(s) with autosomal recessive Charcot-Marie-Tooth disease (PMID: 29858556). This variant is present in population databases (no rsID available, gnomAD 0.01%). |
Institute of Human Genetics, |
RCV000664229 | SCV000787794 | likely pathogenic | Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; | 2018-04-25 | no assertion criteria provided | clinical testing |