Submissions for variant NM_000235.4(LIPA):c.260G>T (p.Gly87Val)

gnomAD frequency: 0.00001  dbSNP: rs587778878

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000191997	SCV000797291	likely pathogenic	Lysosomal acid lipase deficiency	2018-01-19	criteria provided, single submitter	clinical testing
Invitae	RCV001376576	SCV000831923	pathogenic	Wolman disease	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 87 of the LIPA protein (p.Gly87Val). This variant is present in population databases (rs587778878, gnomAD 0.003%). This missense change has been observed in individuals with cholesteryl ester storage disease (CESD) or Wolman disease (PMID: 2129132, 8894696, 11441129, 23424026, 28374935). ClinVar contains an entry for this variant (Variation ID: 88770). 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: 9684740, 11441129). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269917	SCV001450275	pathogenic	not provided	2015-05-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001269917	SCV002756618	pathogenic	not provided	2022-05-18	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect due to significantly reduced enzyme activity compared to wildtype (Pagani et al., 1998; Zschenker et al., 2001; Vinje et al., 2018; Vinje et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26225414, 23424026, 11441129, 28374935, 31589614, 8894696, 31131398, 22138108, 30684275, 9684740, 33857477, 29196158, 21291321)
Fulgent Genetics, Fulgent Genetics	RCV000191997	SCV002810889	pathogenic	Lysosomal acid lipase deficiency	2021-12-30	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000191997	SCV003924300	pathogenic	Lysosomal acid lipase deficiency	2023-05-08	criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003987346	SCV004804781	pathogenic	Cholesteryl ester storage disease	2024-03-17	criteria provided, single submitter	research
FirmaLab, FirmaLab	RCV000191997	SCV000106039	pathogenic	Lysosomal acid lipase deficiency		no assertion criteria provided	clinical testing
GeneReviews	RCV000191997	SCV000246263	not provided	Lysosomal acid lipase deficiency		no assertion provided	literature only
Natera, Inc.	RCV000191997	SCV001453550	pathogenic	Lysosomal acid lipase deficiency	2020-09-16	no assertion criteria provided	clinical testing