ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2152G>A (p.Asp718Asn) (rs119103228)

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
Mayo Clinic Laboratories, Mayo Clinic RCV000001985 SCV000782518 pathogenic Holocarboxylase synthetase deficiency 2016-11-07 criteria provided, single submitter clinical testing
Counsyl RCV000001985 SCV000800478 uncertain significance Holocarboxylase synthetase deficiency 2017-01-24 criteria provided, single submitter clinical testing
Invitae RCV000001985 SCV000834658 likely pathogenic Holocarboxylase synthetase deficiency 2019-09-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 571 of the HLCS protein (p.Asp571Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs119103228, ExAC 0.02%). This variant has been observed in combination with other HLCS variants in individuals affected with holocarboxylase synthetase deficiency (PMID: 8817339, 11735028). ClinVar contains an entry for this variant (Variation ID: 1908). Experimental studies have shown that this missense change disrupts enzyme function in vitro (PMID: 10190325, 10068510). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000001985 SCV000914969 uncertain significance Holocarboxylase synthetase deficiency 2018-11-09 criteria provided, single submitter clinical testing The HLCS c.1711G>A (p.Asp571Asn) variant has been reported in four studies and is found in a total of at least two patients in a compound heterozygous state (Dupuis et al. 1996; Aoki et al. 1999; Yang et al. 2001; Suzuki et al. 2005). Control data are unavailable for this variant, which is reported at a frequency of 0.00008 in the European (non-Finnish) population of the Genome Aggregation Database. Transient expression of the p.Asp571Asn variant, which occurs at a highly conserved residue in a putative biotin-binding region in transformed patient fibroblasts resulted in HCS enzyme activity of 0.1% that of the wild type enzyme (Aoki et al. 1999). Based on the evidence, the p.Asp571Asn variant is classified as a variant of unknown significance but suspicious for holocarboxylase synthetase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000001985 SCV000022143 pathogenic Holocarboxylase synthetase deficiency 1999-02-01 no assertion criteria provided literature only

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.