ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.1808A>G (p.Tyr603Cys)

gnomAD frequency: 0.00002  dbSNP: rs781603756
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669580 SCV000794347 uncertain significance Holocarboxylase synthetase deficiency 2017-09-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000669580 SCV002295729 likely pathogenic Holocarboxylase synthetase deficiency 2022-12-06 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 554029). This missense change has been observed in individual(s) with holocarboxylase synthetase deficiency (PMID: 11735028, 17274881). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs781603756, gnomAD 0.02%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 456 of the HLCS protein (p.Tyr456Cys). 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 expected to disrupt HLCS protein function. 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. Experimental studies have shown that this missense change affects HLCS function (PMID: 11735028).
Baylor Genetics RCV000669580 SCV004199867 likely pathogenic Holocarboxylase synthetase deficiency 2023-02-12 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000669580 SCV005051836 likely pathogenic Holocarboxylase synthetase deficiency 2024-02-01 criteria provided, single submitter curation

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