ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.1480C>T (p.Pro494Ser)

gnomAD frequency: 0.00003  dbSNP: rs556454789
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 RCV001051496 SCV001215651 uncertain significance Holocarboxylase synthetase deficiency 2022-06-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 347 of the HLCS protein (p.Pro347Ser). This variant is present in population databases (rs556454789, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with HLCS-related conditions. ClinVar contains an entry for this variant (Variation ID: 847861). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HLCS protein function. 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.
Breakthrough Genomics, Breakthrough Genomics RCV004693519 SCV005195130 uncertain significance not provided criteria provided, single submitter not provided
Natera, Inc. RCV001051496 SCV001455960 uncertain significance Holocarboxylase synthetase deficiency 2020-01-17 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.