ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.455T>C (p.Leu152Pro)

gnomAD frequency: 0.00001  dbSNP: rs748267444
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Alexion Pharmaceuticals, Inc 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.

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