Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory, |
RCV001174299 | SCV001337431 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV001858530 | SCV002237577 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 587 of the MFN2 protein (p.Pro587Ser). This variant is present in population databases (rs771675874, gnomAD 0.004%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 694952). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. 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 | RCV002399858 | SCV002711707 | uncertain significance | Inborn genetic diseases | 2020-07-28 | criteria provided, single submitter | clinical testing | The p.P587S variant (also known as c.1759C>T), located in coding exon 14 of the MFN2 gene, results from a C to T substitution at nucleotide position 1759. The proline at codon 587 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Athena Diagnostics Inc | RCV002473156 | SCV002771030 | uncertain significance | not provided | 2023-03-08 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function. |
| Genesis Genome Database | RCV000857110 | SCV000999685 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2019-08-14 | no assertion criteria provided | research |