Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Alexion Pharmaceuticals, |
RCV000857259 | SCV000999848 | likely pathogenic | Lysosomal acid lipase deficiency | 2019-06-01 | criteria provided, single submitter | research | |
| Invitae | RCV001869315 | SCV002271486 | likely pathogenic | Wolman disease | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 307 of the LIPA protein (p.Ala307Asp). This variant is present in population databases (rs754964952, gnomAD 0.004%). This missense change has been observed in individual(s) with lysosomal acid lipase deficiency (PMID: 27624512). ClinVar contains an entry for this variant (Variation ID: 695045). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects LIPA function (PMID: 31180157). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Revvity Omics, |
RCV003489942 | SCV003831831 | likely pathogenic | not provided | 2022-10-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001869315 | SCV004020505 | likely pathogenic | Wolman disease | 2023-06-23 | criteria provided, single submitter | clinical testing | Variant summary: LIPA c.920C>A (p.Ala307Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251338 control chromosomes (gnomAD). c.920C>A has been reported in the literature in at least one individual affected with Lysosomal Acid Lipase Deficiency (Himes_2016). These data do not allow any conclusion about variant significance. Functional in vitro assays using cell lysates from stably transfected cells show the variant had <10% LAL activity compared to wild-type (Del Angel_2019). The following publications have been ascertained in the context of this evaluation (PMID: 31180157, 27624512). Three ClinVar submitters have assessed the variant since 2014: all three classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |