Submissions for variant NM_000235.4(LIPA):c.131G>A (p.Trp44Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV002309838	SCV002603717	likely pathogenic	Lysosomal acid lipase deficiency	2022-02-20	criteria provided, single submitter	clinical testing	NM_000235.2(LIPA):c.131G>A(W44*) is expected to be pathogenic in the context of lysosomal acid lipase deficiency. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in LIPA, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Invitae	RCV003598071	SCV004422241	pathogenic	Wolman disease	2023-09-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp44*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LIPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1724570). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.