ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2036C>A (p.Ser679Tyr)

gnomAD frequency: 0.00002  dbSNP: rs777373322
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489053 SCV000577091 uncertain significance not provided 2018-06-22 criteria provided, single submitter clinical testing The S532Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S532Y variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S532Y variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001245310 SCV001418588 uncertain significance Holocarboxylase synthetase deficiency 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 532 of the HLCS protein (p.Ser532Tyr). This variant is present in population databases (rs777373322, gnomAD 0.004%). 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: 426609). 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 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.
Natera, Inc. RCV001245310 SCV002083728 uncertain significance Holocarboxylase synthetase deficiency 2019-10-28 no assertion criteria provided clinical testing

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