ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.931G>A (p.Gly311Arg)

dbSNP: rs1589548972
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Alexion, Astrazeneca Rare Disease, Astrazeneca RCV000857257 SCV000999846 likely pathogenic Lysosomal acid lipase deficiency 2019-06-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323742 SCV004030098 likely pathogenic Wolman disease 2023-07-25 criteria provided, single submitter clinical testing Variant summary: LIPA c.931G>A (p.Gly311Arg) 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 was absent in 251358 control chromosomes. To our knowledge, no occurrence of c.931G>A in individuals affected with Lysosomal Acid Lipase Deficiency has been reported. At least one publication reports experimental evidence evaluating an impact on protein function, with enzymatic activity of the variant protein being <10% of normal activity (Del Angel_2019). The following publication has been ascertained in the context of this evaluation (PMID: 31180157). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Ambry Genetics RCV004994071 SCV005608169 uncertain significance Cardiovascular phenotype 2024-07-23 criteria provided, single submitter clinical testing The p.G311R variant (also known as c.931G>A), located in coding exon 8 of the LIPA gene, results from a G to A substitution at nucleotide position 931. The glycine at codon 311 is replaced by arginine, an amino acid with dissimilar properties. In an assay testing LIPA function, this variant showed a functionally abnormal result (Del Angel G et al. Hum Mutat, 2019 Nov;40:2007-2020). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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