Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001313180 | SCV001503663 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2Z | 2022-08-22 | 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 not expected to disrupt MORC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1014447). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. This variant is present in population databases (rs143046507, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 484 of the MORC2 protein (p.Arg484His). |
Institute of Human Genetics, |
RCV001843582 | SCV002103080 | uncertain significance | not provided | 2021-12-14 | criteria provided, single submitter | clinical testing | PP2 |
Ambry Genetics | RCV002543620 | SCV003602562 | uncertain significance | Inborn genetic diseases | 2022-03-16 | criteria provided, single submitter | clinical testing | The c.1451G>A (p.R484H) alteration is located in exon 15 (coding exon 15) of the MORC2 gene. This alteration results from a G to A substitution at nucleotide position 1451, causing the arginine (R) at amino acid position 484 to be replaced by a histidine (H). Based on data from gnomAD, the A allele has an overall frequency of <0.01% (4/282848) total alleles studied. The highest observed frequency was 0.01% (3/24964) of African alleles. This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |