Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Alexion Pharmaceuticals, |
RCV000857269 | SCV000999858 | likely pathogenic | Lysosomal acid lipase deficiency | 2019-06-01 | criteria provided, single submitter | research | |
Invitae | RCV001858535 | SCV002233593 | pathogenic | Wolman disease | 2023-04-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects LIPA function (PMID: 29196158, 31131398). 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. ClinVar contains an entry for this variant (Variation ID: 695055). This variant is also known as His108Arg. This missense change has been observed in individual(s) with cholesteryl ester storage disease (PMID: 9633819, 30684275, 31113597). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 129 of the LIPA protein (p.His129Arg). |