Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000530299 | SCV000653551 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate F | 2023-06-27 | 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 GNB4 protein function. ClinVar contains an entry for this variant (Variation ID: 473893). This variant has not been reported in the literature in individuals affected with GNB4-related conditions. This variant is present in population databases (rs752762550, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 267 of the GNB4 protein (p.Asp267Asn). |
| Ambry Genetics | RCV002530228 | SCV003550934 | uncertain significance | Inborn genetic diseases | 2022-01-19 | criteria provided, single submitter | clinical testing | The c.799G>A (p.D267N) alteration is located in exon 9 (coding exon 8) of the GNB4 gene. This alteration results from a G to A substitution at nucleotide position 799, causing the aspartic acid (D) at amino acid position 267 to be replaced by an asparagine (N). Based on data from the Genome Aggregation Database (gnomAD), the c.799G>A alteration was observed in <0.001% (1/251,382) of total alleles studied. 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. |