ClinVar Miner

Submissions for variant NM_024665.7(TBL1XR1):c.346G>T (p.Ala116Ser)

gnomAD frequency: 0.00006  dbSNP: rs372813783
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541283 SCV000645304 uncertain significance Pierpont syndrome 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 116 of the TBL1XR1 protein (p.Ala116Ser). This variant is present in population databases (rs372813783, gnomAD 0.01%). This missense change has been observed in individual(s) with epilepsy (PMID: 25102098). ClinVar contains an entry for this variant (Variation ID: 468536). 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 TBL1XR1 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.
CeGaT Center for Human Genetics Tuebingen RCV001092439 SCV001248953 likely benign not provided 2024-01-01 criteria provided, single submitter clinical testing TBL1XR1: PP2, BP4, BS1
GeneDx RCV001092439 SCV001757005 likely benign not provided 2020-03-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25102098)
Ambry Genetics RCV002341379 SCV002618796 uncertain significance Inborn genetic diseases 2018-06-20 criteria provided, single submitter clinical testing The p.A116S variant (also known as c.346G>T), located in coding exon 3 of the TBL1XR1 gene, results from a G to T substitution at nucleotide position 346. The alanine at codon 116 is replaced by serine, an amino acid with similar properties. This variant was identified in a cohort of individuals with epilepsy; however, additional details were not provided (Saitsu H et al. J. Hum. Genet., 2014 Oct;59:581-3). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear.

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