ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.881T>C (p.Leu294Ser)

dbSNP: rs756310979
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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 RCV000857260 SCV000999849 likely pathogenic Lysosomal acid lipase deficiency 2019-06-01 criteria provided, single submitter research
Invitae RCV003495186 SCV004295333 likely pathogenic Wolman disease 2023-03-18 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects LIPA function (PMID: 8894696, 29196158, 31131398, 31180157). 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 not expected to disrupt LIPA protein function. ClinVar contains an entry for this variant (Variation ID: 695046). This variant is also known as L273S. This missense change has been observed in individual(s) with cholesteryl ester storage disease (PMID: 8894696, 28881270). 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 (rs756310979, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 294 of the LIPA protein (p.Leu294Ser).

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