ClinVar Miner

Submissions for variant NM_006859.4(LIAS):c.944G>A (p.Arg315His) (rs145535775)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000712220 SCV000241654 uncertain significance not provided 2016-11-23 criteria provided, single submitter clinical testing The R315H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is highly conserved across species. A missense variant in a nearby residue (M310T) has been reported in the Human Gene Mutation Database in association with a LIAS-related disorder (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R315H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether the R315H variant is a pathogenic variant or a rare benign variant.
Invitae RCV000650017 SCV000771854 uncertain significance Pyruvate dehydrogenase lipoic acid synthetase deficiency 2020-09-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 315 of the LIAS protein (p.Arg315His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs145535775, ExAC 0.1%). This variant has not been reported in the literature in individuals with LIAS-related disease. ClinVar contains an entry for this variant (Variation ID: 206042). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
Athena Diagnostics Inc RCV000712220 SCV000842658 uncertain significance not provided 2017-09-18 criteria provided, single submitter clinical testing

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