ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2500G>A (p.Val834Ile)

gnomAD frequency: 0.00007  dbSNP: rs145648338
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185963 SCV000238921 uncertain significance not provided 2014-08-06 criteria provided, single submitter clinical testing Mutations in the HLCS gene are associated with the autosomal recessive disorder holocarboxylase synthetase deficiency. The V687I variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V687I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000634876 SCV000756233 uncertain significance Holocarboxylase synthetase deficiency 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 687 of the HLCS protein (p.Val687Ile). This variant is not present in population databases (gnomAD no frequency). 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: 203771). 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 not 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 RCV004020255 SCV004882386 uncertain significance Inborn genetic diseases 2023-12-09 criteria provided, single submitter clinical testing The c.2059G>A (p.V687I) alteration is located in exon 12 (coding exon 9) of the HLCS gene. This alteration results from a G to A substitution at nucleotide position 2059, causing the valine (V) at amino acid position 687 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000634876 SCV001453938 uncertain significance Holocarboxylase synthetase deficiency 2020-03-17 no assertion criteria provided clinical testing

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