Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010100 | SCV001170248 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-01 | criteria provided, single submitter | clinical testing | The p.A39V variant (also known as c.116C>T), located in coding exon 1 of the HOXB13 gene, results from a C to T substitution at nucleotide position 116. The alanine at codon 39 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001858487 | SCV002107641 | uncertain significance | not provided | 2023-03-18 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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: 690532). 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. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 39 of the HOXB13 protein (p.Ala39Val). |
| Laboratory of Virology, |
RCV000855835 | SCV000993826 | uncertain significance | Prostate cancer, hereditary, 1 | no assertion criteria provided | clinical testing | ||
| Prevention |
RCV003928320 | SCV004746723 | uncertain significance | HOXB13-related disorder | 2023-12-19 | no assertion criteria provided | clinical testing | The HOXB13 c.116C>T variant is predicted to result in the amino acid substitution p.Ala39Val. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/690532/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |