Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000694545 | SCV000822996 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 12 of the MFN2 protein (p.Val12Ile). This variant is present in population databases (rs367715413, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 34190362; internal data). ClinVar contains an entry for this variant (Variation ID: 573004). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MFN2 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV002458249 | SCV002615094 | uncertain significance | Inborn genetic diseases | 2019-11-12 | criteria provided, single submitter | clinical testing | The p.V12I variant (also known as c.34G>A), located in coding exon 1 of the MFN2 gene, results from a G to A substitution at nucleotide position 34. The valine at codon 12 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |