ClinVar Miner

Submissions for variant NM_006859.4(LIAS):c.637A>G (p.Thr213Ala) (rs374709255)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188057 SCV000241660 uncertain significance not provided 2014-01-17 criteria provided, single submitter clinical testing p.Thr213Ala (ACT>GCT): c.637 A>G in exon 7 of the LIAS gene (NM_006859.2). The Thr213Ala missense change in the LIAS gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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. This variant is a non-conservative amino acid substitution of a polar Threonine residue with a non-polar Alanine residue at a position that is highly conserved across species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Thr213Ala is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI,EPILEPSY panel(s).
Invitae RCV000822700 SCV000963513 uncertain significance Pyruvate dehydrogenase lipoic acid synthetase deficiency 2019-11-07 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 213 of the LIAS protein (p.Thr213Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs374709255, ExAC 0.01%). This variant has not been reported in the literature in individuals with LIAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 206048). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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