Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001362178 | SCV001558182 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 637 of the MFN2 protein (p.Ser637Phe). This variant is not present in population databases (gnomAD no frequency). 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. 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 expected to disrupt MFN2 protein function. ClinVar contains an entry for this variant (Variation ID: 637714). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. |
| Ambry Genetics | RCV002406718 | SCV002720557 | uncertain significance | Inborn genetic diseases | 2022-09-30 | criteria provided, single submitter | clinical testing | The p.S637F variant (also known as c.1910C>T), located in coding exon 15 of the MFN2 gene, results from a C to T substitution at nucleotide position 1910. The serine at codon 637 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been detected in individuals with Charcot-Marie-Tooth type 2; however, clinical details were limited (Hauw F et al. Eur J Neurol, 2021 09;28:2846-2854; Bombelli F et al. JAMA Neurol, 2014 Aug;71:1036-42). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Inherited Neuropathy Consortium | RCV000790005 | SCV000929395 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |