Submissions for variant NM_000235.4(LIPA):c.891C>T (p.Ser297=)

gnomAD frequency: 0.00039  dbSNP: rs145066614

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000673075	SCV000365980	uncertain significance	Lysosomal acid lipase deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000322362	SCV000365981	uncertain significance	Wolman disease	2016-06-14	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000594326	SCV000704061	uncertain significance	not provided	2016-11-28	criteria provided, single submitter	clinical testing
Counsyl	RCV000673075	SCV000798243	uncertain significance	Lysosomal acid lipase deficiency	2018-03-07	criteria provided, single submitter	clinical testing
Invitae	RCV000322362	SCV001031295	likely benign	Wolman disease	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000594326	SCV001786514	uncertain significance	not provided	2020-10-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28502505)
Ambry Genetics	RCV002374515	SCV002687535	likely benign	Cardiovascular phenotype	2022-04-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003950011	SCV004769259	likely benign	LIPA-related condition	2021-04-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).