Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497343 | SCV000590682 | uncertain significance | not provided | 2017-06-21 | criteria provided, single submitter | clinical testing | The R569C variant in the MORC2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R569C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R569C variant is a non-conservative amino acid substitution, which occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R569C as a variant of uncertain significance, |
| Ambry Genetics | RCV002399424 | SCV002710473 | uncertain significance | Inborn genetic diseases | 2019-12-03 | criteria provided, single submitter | clinical testing | The p.R569C variant (also known as c.1705C>T), located in coding exon 17 of the MORC2 gene, results from a C to T substitution at nucleotide position 1705. The arginine at codon 569 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV003754867 | SCV004459270 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2Z | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 569 of the MORC2 protein (p.Arg569Cys). This variant is present in population databases (rs267606222, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 81950). 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 MORC2 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. |