ClinVar Miner

Submissions for variant NM_006859.4(LIAS):c.850G>A (p.Glu284Lys)

gnomAD frequency: 0.00001  dbSNP: rs796052699
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188048 SCV000241651 uncertain significance not provided 2014-07-01 criteria provided, single submitter clinical testing p.Glu284Lys (GAG>AAG): c.850 G>A in exon 8 of the LIAS gene (NM_006859.2). A variant of unknown significance has been identified in the LIAS gene. The E284K variant 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. The E284K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported in association with LIAS-related disorders. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000801566 SCV000941346 uncertain significance Lipoic acid synthetase deficiency 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 284 of the LIAS protein (p.Glu284Lys). This variant is present in population databases (rs796052699, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with LIAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 206039). 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 disruptive. 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.
GenomeConnect - Invitae Patient Insights Network RCV000801566 SCV001749967 not provided Lipoic acid synthetase deficiency no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 10-23-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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