ClinVar Miner

Submissions for variant NM_006859.4(LIAS):c.122A>G (p.Asn41Ser)

gnomAD frequency: 0.00003  dbSNP: rs761295906
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188053 SCV000241656 uncertain significance not provided 2014-03-06 criteria provided, single submitter clinical testing p.Asn41Ser (AAT>AGT): c.122 A>G in exon 2 of the LIAS gene (NM_006859.2). A variant of unknown significance has been identified in the LIAS gene. The Asn41Ser 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 Asn41Ser variant alters a position that is conserved in mammals in the LIAS protein. However, the variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and in silico analysis predicts this variant likely does not alter the protein structure/function. 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV000548048 SCV000652147 uncertain significance Lipoic acid synthetase deficiency 2022-08-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 41 of the LIAS protein (p.Asn41Ser). This variant is present in population databases (rs761295906, gnomAD 0.003%). 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: 206044). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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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