ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.1985G>A (p.Ser662Asn)

gnomAD frequency: 0.00002  dbSNP: rs773398782
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital RCV000492067 SCV000579458 likely pathogenic Holocarboxylase synthetase deficiency 2017-06-17 criteria provided, single submitter clinical testing the patient carry compound heterozygote mutation, one is confirmed to be pathogenic. [c.1522C>T (p.Arg508Trp)]+[ c.1544G>A(p.Ser515Asn)]
Ambry Genetics RCV002527063 SCV003729164 uncertain significance Inborn genetic diseases 2022-05-30 criteria provided, single submitter clinical testing The c.1544G>A (p.S515N) alteration is located in exon 9 (coding exon 6) of the HLCS gene. This alteration results from a G to A substitution at nucleotide position 1544, causing the serine (S) at amino acid position 515 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000492067 SCV004199848 pathogenic Holocarboxylase synthetase deficiency 2024-03-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000492067 SCV005845617 pathogenic Holocarboxylase synthetase deficiency 2024-10-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 515 of the HLCS protein (p.Ser515Asn). This variant is present in population databases (rs773398782, gnomAD 0.01%). This missense change has been observed in individuals with holocarboxylase synthetase deficiency (PMID: 36890565). ClinVar contains an entry for this variant (Variation ID: 428585). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt HLCS protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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