ClinVar Miner

Submissions for variant NM_006361.6(HOXB13):c.366C>A (p.Ser122Arg)

dbSNP: rs8556
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115970 SCV000149879 uncertain significance not provided 2024-08-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28272408)
Ambry Genetics RCV001020842 SCV001182374 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-29 criteria provided, single submitter clinical testing The p.S122R variant (also known as c.366C>A), located in coding exon 1 of the HOXB13 gene, results from a C to A substitution at nucleotide position 366. The serine at codon 122 is replaced by arginine, an amino acid with dissimilar properties. This alteration was predicted deleterious based on several computational models and in silico comparative homology modeling of protein structure, which showed that this variant results in reduced protein stability (Chandrasekaran G et al. Sci. Rep. 2017 Mar;7:43830). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by Bayesdel in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000115970 SCV001231419 uncertain significance not provided 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 122 of the HOXB13 protein (p.Ser122Arg). This variant is present in population databases (rs8556, gnomAD 0.01%). 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: 128032). 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.
Fulgent Genetics, Fulgent Genetics RCV005016397 SCV005644234 uncertain significance Prostate cancer, hereditary, 9 2024-04-18 criteria provided, single submitter clinical testing

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