ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.733A>T (p.Thr245Ser)

gnomAD frequency: 0.00002  dbSNP: rs764926275
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002000339 SCV002257749 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2022-07-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 245 of the HMGCL protein (p.Thr245Ser). This variant is present in population databases (rs764926275, gnomAD 0.003%). 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: 1480632). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002573537 SCV003760621 uncertain significance Inborn genetic diseases 2021-10-18 criteria provided, single submitter clinical testing The c.733A>T (p.T245S) alteration is located in exon 7 (coding exon 7) of the HMGCL gene. This alteration results from a A to T substitution at nucleotide position 733, causing the threonine (T) at amino acid position 245 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002000339 SCV004173411 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter 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.