Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575060 | SCV000669485 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-06 | criteria provided, single submitter | clinical testing | The p.R217H variant (also known as c.650G>A), located in coding exon 2 of the HOXB13 gene, results from a G to A substitution at nucleotide position 650. The arginine at codon 217 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001320504 | SCV001511293 | uncertain significance | not provided | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 217 of the HOXB13 protein (p.Arg217His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 483506). 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 HOXB13 protein function. 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 | RCV001320504 | SCV005625207 | uncertain significance | not provided | 2024-01-23 | criteria provided, single submitter | clinical testing | The HOXB13 c.650G>A (p.Arg217His) variant has not been reported in individuals with HOXB13-related conditions in the published literature. The frequency of this variant in the general population, 0.000008 (2/249302 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Fulgent Genetics, |
RCV005018983 | SCV005644228 | uncertain significance | Prostate cancer, hereditary, 9 | 2024-05-14 | criteria provided, single submitter | clinical testing |