ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2135G>A (p.Arg712Gln)

gnomAD frequency: 0.00001  dbSNP: rs769446135
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000634875 SCV000756232 uncertain significance Holocarboxylase synthetase deficiency 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 565 of the HLCS protein (p.Arg565Gln). This variant is present in population databases (rs769446135, gnomAD 0.05%). 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: 529439). 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.
Ambry Genetics RCV002529826 SCV003737067 uncertain significance Inborn genetic diseases 2022-01-12 criteria provided, single submitter clinical testing The c.1694G>A (p.R565Q) alteration is located in exon 10 (coding exon 7) of the HLCS gene. This alteration results from a G to A substitution at nucleotide position 1694, causing the arginine (R) at amino acid position 565 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000634875 SCV002083723 uncertain significance Holocarboxylase synthetase deficiency 2019-10-28 no assertion criteria provided clinical testing

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