Submissions for variant NM_000235.4(LIPA):c.594dup (p.Ala199fs)

dbSNP: rs780495201

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000000100	SCV000485753	likely pathogenic	Lysosomal acid lipase deficiency	2016-11-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000000099	SCV001401612	pathogenic	Wolman disease	2023-10-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala199Cysfs*13) in the LIPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIPA are known to be pathogenic (PMID: 23485521). This variant is present in population databases (rs780495201, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with LIPA-related conditions (PMID: 8146180, 16255772). ClinVar contains an entry for this variant (Variation ID: 80). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001549751	SCV001769960	pathogenic	not provided	2020-01-09	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 16255772, 30315827, 8146180)
Revvity Omics, Revvity	RCV001549751	SCV003820973	pathogenic	not provided	2022-04-29	criteria provided, single submitter	clinical testing
OMIM	RCV000000099	SCV000020242	pathogenic	Wolman disease	1994-03-29	no assertion criteria provided	literature only
OMIM	RCV000524544	SCV000020243	pathogenic	Cholesteryl ester storage disease	1994-03-29	no assertion criteria provided	literature only
Natera, Inc.	RCV000000100	SCV002091388	pathogenic	Lysosomal acid lipase deficiency	2020-09-22	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004734493	SCV005362514	pathogenic	LIPA-related disorder	2024-09-21	no assertion criteria provided	clinical testing	The LIPA c.594dupT variant is predicted to result in a frameshift and premature protein termination (p.Ala199Cysfs*13). This variant, in combination with a second pathogenic variant, has reported to be causative for Wolman disease (Anderson et al., 1994. PubMed ID: 8146180; Bernstein DL et al 2013. PubMed ID: 23485521; Tadiboyina VT et al 2005. PubMed ID: 16255772). This variant has been reported as c.634insT and c.594insT. This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-90984929-C-CA). Frameshift variants in LIPA are expected to be pathogenic. This variant is interpreted as pathogenic.