ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.182A>G (p.Asp61Gly)

gnomAD frequency: 0.00010  dbSNP: rs143981931
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002657889 SCV002978900 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2024-10-08 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 61 of the HMGCL protein (p.Asp61Gly). This variant is present in population databases (rs143981931, gnomAD 0.02%). 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: 1935885). 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.
GeneDx RCV003443065 SCV004170403 uncertain significance not provided 2023-05-01 criteria provided, single submitter clinical testing 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
Genome-Nilou Lab RCV002657889 SCV004172736 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004066647 SCV004884677 uncertain significance Inborn genetic diseases 2024-01-03 criteria provided, single submitter clinical testing The c.182A>G (p.D61G) alteration is located in exon 3 (coding exon 3) of the HMGCL gene. This alteration results from a A to G substitution at nucleotide position 182, causing the aspartic acid (D) at amino acid position 61 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.