ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.294C>G (p.Asn98Lys)

gnomAD frequency: 0.00001  dbSNP: rs767688436
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000598187 SCV000707928 uncertain significance not provided 2017-04-18 criteria provided, single submitter clinical testing
Alexion Pharmaceuticals, Inc 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).

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