ClinVar Miner

Submissions for variant NM_025243.4(SLC19A3):c.865A>G (p.Thr289Ala)

gnomAD frequency: 0.00012  dbSNP: rs746272588
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200692 SCV000252267 uncertain significance not provided 2018-09-10 criteria provided, single submitter clinical testing p.Thr289Ala (ACA>GCA): c.865 A>G in exon 3 in the SLC19A3 gene (NM_025243.3). The T289A variant in the SLC19A3 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. This variant is a non-conservative amino acid substitution as a polar Threonine residue is replaced with a non-polar Alanine residue at a position that is well conserved across species and is located within the transmembrane helical domain of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. The T289A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret T289A as a variant of unknown significance. The variant is found in SLC19A3, panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001853198 SCV002274627 uncertain significance Biotin-responsive basal ganglia disease 2022-07-23 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 289 of the SLC19A3 protein (p.Thr289Ala). This variant is present in population databases (rs746272588, gnomAD 0.01%). This missense change has been observed in individual(s) with a neurocognitive disorder (PMID: 26077850). ClinVar contains an entry for this variant (Variation ID: 215157). 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 SLC19A3 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.

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