Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Alexion Pharmaceuticals, |
RCV000857253 | SCV000999842 | likely pathogenic | Lysosomal acid lipase deficiency | 2019-06-01 | criteria provided, single submitter | research | |
Invitae | RCV001382524 | SCV001581347 | pathogenic | Wolman disease | 2023-03-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 695039). This missense change has been observed in individual(s) with lysosomal acid lipase (LAL) deficiency (PMID: 28881270, 30684275). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 345 of the LIPA protein (p.Asp345Asn). |