ClinVar Miner

Submissions for variant NM_006859.4(LIAS):c.746G>A (p.Arg249His) (rs144133667)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000023604 SCV000825424 uncertain significance Pyruvate dehydrogenase lipoic acid synthetase deficiency 2018-04-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 249 of the LIAS protein (p.Arg249His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs144133667, ExAC 0.002%). This variant has been reported in an individual affected with neonatal-onset epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine (PMID: 22152680). ClinVar contains an entry for this variant (Variation ID: 30629). Experimental studies have shown that this missense change alters lipoic acid metabolism (PMID: 2152680, 27923773). 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.
OMIM RCV000023604 SCV000044895 pathogenic Pyruvate dehydrogenase lipoic acid synthetase deficiency 2011-12-09 no assertion criteria provided literature only

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