ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.347G>A (p.Arg116His)

gnomAD frequency: 0.00021  dbSNP: rs147906427
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000700818 SCV000829590 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2022-08-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 116 of the HMGCS2 protein (p.Arg116His). This variant is present in population databases (rs147906427, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with HMGCS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 577951). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HMGCS2 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.
GeneDx RCV004760734 SCV005368818 uncertain significance not provided 2023-06-16 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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