ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.595G>C (p.Glu199Gln)

dbSNP: rs149526487
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002461845 SCV002756884 uncertain significance not provided 2022-05-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
Labcorp Genetics (formerly Invitae), Labcorp RCV003103115 SCV002946992 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 199 of the HMGCL protein (p.Glu199Gln). This variant is present in population databases (rs149526487, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with HMGCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1800706). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt HMGCL protein function with a negative predictive value of 80%. 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.
Genome-Nilou Lab RCV003103115 SCV004173208 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing

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