Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001215016 | SCV001386735 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2Z | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 535 of the MORC2 protein (p.Arg535Trp). This variant is present in population databases (rs576981610, gnomAD 0.007%). 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: 944588). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | RCV002402640 | SCV002709175 | uncertain significance | Inborn genetic diseases | 2022-03-22 | criteria provided, single submitter | clinical testing | The p.R535W variant (also known as c.1603C>T), located in coding exon 16 of the MORC2 gene, results from a C to T substitution at nucleotide position 1603. The arginine at codon 535 is replaced by tryptophan, an amino acid with dissimilar 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. |