Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001883936 | SCV002146911 | uncertain significance | Holocarboxylase synthetase deficiency | 2021-10-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with HLCS-related conditions. 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. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 490 of the HLCS protein (p.Pro490Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. |