Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Alexion Pharmaceuticals, |
RCV000857266 | SCV000999855 | likely pathogenic | Lysosomal acid lipase deficiency | 2019-06-01 | criteria provided, single submitter | research | |
Invitae | RCV001379703 | SCV001577551 | pathogenic | Wolman disease | 2023-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 152 of the LIPA protein (p.Leu152Pro). This variant is present in population databases (rs748267444, gnomAD 0.0009%). This missense change has been observed in individual(s) with LAL deficiency (PMID: 24993530, 31180157). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 695052). 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 LIPA protein function. Experimental studies have shown that this missense change affects LIPA function (PMID: 31180157). For these reasons, this variant has been classified as Pathogenic. |