ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.283T>A (p.Trp95Arg)

dbSNP: rs1554866097
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669223 SCV000793954 uncertain significance Lysosomal acid lipase deficiency 2017-09-05 criteria provided, single submitter clinical testing
Alexion Pharmaceuticals, Inc RCV000669223 SCV000999867 likely pathogenic Lysosomal acid lipase deficiency 2019-06-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271556 SCV002556142 likely pathogenic Wolman disease 2022-06-24 criteria provided, single submitter clinical testing Variant summary: LIPA c.283T>A (p.Trp95Arg) results in a non-conservative amino acid change located in the alpha/beta hydrolase fold-1 domain (IPR000073) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251384 control chromosomes (gnomAD). c.283T>A has been reported in the literature in at least one individual affected with Lysosomal Acid Lipase Deficiency (Elleder_1999). In an enzyme activity assay, the variant was found to have 5% of wild-type activity, indicating that it has a negative impact on protein function (Vinje_2018). A follow-up study also showed that the variant resulted in a protein that was not efficiently transported out of the ER (Vinje_2019). Two assessments for this variant have been submitted to ClinVar after 2014. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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