Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565367 | SCV000673589 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-16 | criteria provided, single submitter | clinical testing | The p.G176R variant (also known as c.526G>C), located in coding exon 1 of the HOXB13 gene, results from a G to C substitution at nucleotide position 526. The glycine at codon 176 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly 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. |
| Fulgent Genetics, |
RCV000764135 | SCV000895110 | uncertain significance | Prostate cancer, hereditary, 9 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001203958 | SCV001375143 | uncertain significance | not provided | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 176 of the HOXB13 protein (p.Gly176Arg). This variant is present in population databases (rs747003841, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HOXB13-related conditions. ClinVar contains an entry for this variant (Variation ID: 485694). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt HOXB13 protein function with a negative predictive value of 80%. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001203958 | SCV005625204 | uncertain significance | not provided | 2023-12-05 | criteria provided, single submitter | clinical testing | The HOXB13 c.526G>C (p.Gly176Arg) variant has not been reported in individuals with HOXB13-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251442 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |