Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000598187 | SCV000707928 | uncertain significance | not provided | 2017-04-18 | criteria provided, single submitter | clinical testing | |
Alexion Pharmaceuticals, |
RCV000857276 | SCV000999866 | likely pathogenic | Lysosomal acid lipase deficiency | 2019-06-01 | criteria provided, single submitter | research | |
Invitae | RCV001867978 | SCV002271460 | pathogenic | Wolman disease | 2023-01-04 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs767688436, gnomAD 0.009%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 98 of the LIPA protein (p.Asn98Lys). This missense change has been observed in individual(s) with LIPA-related conditions (PMID: 25624737). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. 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: 501531). |