ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.754A>T (p.Ile252Leu) (rs147493628)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000887810 SCV000365982 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 Clinical Services Laboratory,Illumina RCV000287212 SCV000365983 uncertain significance Wolman disease 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000478562 SCV000572892 uncertain significance not specified 2017-02-10 criteria provided, single submitter clinical testing The I252L variant in the LIPA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I252L variant is observed in 155/66100 (0.2%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The I252L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I252L as a variant of uncertain significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000478562 SCV000702213 likely benign not specified 2017-04-13 criteria provided, single submitter clinical testing
Invitae RCV000287212 SCV001031396 likely benign Wolman disease 2020-12-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV000887810 SCV001456941 likely benign Lysosomal acid lipase deficiency 2020-04-11 no assertion criteria provided clinical testing

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