Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001342749 | SCV001536694 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2Z | 2020-10-28 | criteria provided, single submitter | clinical testing | 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 MORC2 protein function. This variant has not been reported in the literature in individuals with MORC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 268 of the MORC2 protein (p.Ser268Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. |
| Ambry Genetics | RCV002419009 | SCV002680029 | uncertain significance | Inborn genetic diseases | 2021-01-07 | criteria provided, single submitter | clinical testing | The p.S268P variant (also known as c.802T>C), located in coding exon 9 of the MORC2 gene, results from a T to C substitution at nucleotide position 802. The serine at codon 268 is replaced by proline, 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. |