Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519202 | SCV000617756 | likely pathogenic | not provided | 2017-07-10 | criteria provided, single submitter | clinical testing | The V273G variant has been previously reported to segregate with disease in multiple affected individuals from a single large family with CMT (Lawson et al., 2005). The V273G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a conserved position within the dynamin type G domain of the MFN2 protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. |
Invitae | RCV000689677 | SCV000817340 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2019-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with glycine at codon 273 of the MFN2 protein (p.Val273Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot-Marie-Tooth disease (CMT) in a large family (PMID: 16043786). ClinVar contains an entry for this variant (Variation ID: 449524). Experimental studies have shown that this missense change does not affect mitofusin expression, mitochondrial morphology, ultrastructure, mtDNA content, and respiratory capacity in fibroblasts (PMID: 18316077). 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. |
Inherited Neuropathy Consortium | RCV000789395 | SCV000928750 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |