ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.602C>A (p.Ser201Tyr)

gnomAD frequency: 0.00001  dbSNP: rs760106433
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522404 SCV000616740 pathogenic not provided 2020-06-01 criteria provided, single submitter clinical testing Functional analysis in E.coli found that this variant is associated with no detectable residual enzyme activity (Casals et al., 2003).; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12746442)
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000672903 SCV002818465 pathogenic Deficiency of hydroxymethylglutaryl-CoA lyase 2022-12-30 criteria provided, single submitter clinical testing A Homozygous missense variation in exon 7 of the HMGCL gene that results in the amino acid substitution of Tyrosine for Serine at codon 201 was detected. The observed variation lies in the BAR domain of APPL family of HMGCL protien and has previously been reported in patients affected with HMG-CoA lyase deficiency. The c.602C>A (p.Ser201Tyr) variant has not been reported in the 1000 genomes and gnomAD databases and has a minor allele frequency of 0.01% in our internal database. The in silico prediction of the variant are possibly damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic.
Genome-Nilou Lab RCV000672903 SCV004173097 pathogenic Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV000672903 SCV004199888 pathogenic Deficiency of hydroxymethylglutaryl-CoA lyase 2023-09-20 criteria provided, single submitter clinical testing
Counsyl RCV000672903 SCV000798055 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2018-02-21 no assertion criteria provided clinical testing

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.