ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2268_2270del (p.Thr757del)

dbSNP: rs1555882090
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
Counsyl RCV000671802 SCV000796822 uncertain significance Holocarboxylase synthetase deficiency 2018-01-02 criteria provided, single submitter clinical testing
Invitae RCV000671802 SCV003443862 uncertain significance Holocarboxylase synthetase deficiency 2023-10-13 criteria provided, single submitter clinical testing This variant, c.1827_1829del, results in the deletion of 1 amino acid(s) of the HLCS protein (p.Thr610del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with holocarboxylase synthetase deficiency (PMID: 10190325). ClinVar contains an entry for this variant (Variation ID: 555891). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects HLCS function (PMID: 10190325, 24239178). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230571 SCV003928972 uncertain significance not specified 2023-04-04 criteria provided, single submitter clinical testing Variant summary: HLCS c.1827_1829delTAC (p.Thr610del) results in an in-frame deletion that is predicted to remove one amino acids from the Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL), catalytic domain (IPR004143) of the encoded protein. The variant was absent in 251496 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1827_1829delTAC has been reported in the literature in a homozygous individual affected with late onset Holocarboxylase Synthetase Deficiency with mild phenotypes (example: Aoki_1999). These report(s) do not provide unequivocal conclusions about association of the variant with Holocarboxylase Synthetase Deficiency. Experimental studies have shown this variant had comparable activity to Wild-type protein (Aoki_1999 and Sakamoto_1999) but the Vmax was increased by ~3 fold ( Sakamoto_1999). Additionally, Trujillo-Gonzalez_2014 have shown that this variant fail to restore the biotinylation of acetyl-CoA carboxylase biotin carboxyl carrier protein (BCCP) at 42C using a bacterial expression vector. These results are not sufficient to conclusively determine the role of this variant in disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.