Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002947968 | SCV003269273 | uncertain significance | Holocarboxylase synthetase deficiency | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 21 of the HLCS protein (p.Leu21Trp). This variant is present in population databases (rs753272133, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with HLCS-related conditions. 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. |