ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.256C>T (p.His86Tyr)

gnomAD frequency: 0.00002  dbSNP: rs749180806
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671520 SCV000796504 uncertain significance Lysosomal acid lipase deficiency 2017-12-27 criteria provided, single submitter clinical testing
Alexion Pharmaceuticals, Inc RCV000671520 SCV000999868 likely pathogenic Lysosomal acid lipase deficiency 2019-06-01 criteria provided, single submitter research
Invitae RCV001868255 SCV002131805 uncertain significance Wolman disease 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 86 of the LIPA protein (p.His86Tyr). This variant is present in population databases (rs749180806, gnomAD 0.01%). This missense change has been observed in individual(s) with lysosomal acid lipase deficiency (PMID: 28220406). ClinVar contains an entry for this variant (Variation ID: 555658). 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). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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