ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.398del (p.Leu132_Ser133insTer)

gnomAD frequency: 0.00008  dbSNP: rs756016704
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000368412 SCV000344457 pathogenic not provided 2018-01-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001376636 SCV000941771 pathogenic Wolman disease 2024-10-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser133*) 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 present in population databases (rs756016704, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with Wolman disease (PMID: 24832708, 28220406). ClinVar contains an entry for this variant (Variation ID: 289986). For these reasons, this variant has been classified as Pathogenic.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV000801965 SCV001554463 pathogenic Lysosomal acid lipase deficiency 2021-04-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000801965 SCV002060124 pathogenic Lysosomal acid lipase deficiency 2021-11-08 criteria provided, single submitter clinical testing NM_000235.2(LIPA):c.398delC(S133*) is a nonsense variant classified as pathogenic in the context of lysosomal acid lipase deficiency. S133* has been observed in cases with relevant disease (PMID: 11441129). Functional assessments of this variant are available in the literature (PMID: 11441129). S133* has been observed in population frequency databases (gnomAD: NFE 0.004%). In summary, NM_000235.2(LIPA):c.398delC(S133*) is a nonsense variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Fulgent Genetics, Fulgent Genetics RCV005003614 SCV002813880 pathogenic Wolman disease; Cholesteryl ester storage disease 2024-05-06 criteria provided, single submitter clinical testing
GeneDx RCV000368412 SCV005079967 pathogenic not provided 2024-02-28 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33726816, 26913919, 23485521, 11441129, Gashoot2024[case_report], 33857477, 30684275, 24832708, 28220406)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001376636 SCV005204271 pathogenic Wolman disease 2024-06-13 criteria provided, single submitter clinical testing Variant summary: LIPA c.398delC (p.Ser133X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 251418 control chromosomes (gnomAD). c.398delC has been reported in the literature in multiple individuals affected with Lysosomal Acid Lipase Deficiency (Zschenker_2001, Poinsot_2016), including homozygotes. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33857477, 11441129). ClinVar contains an entry for this variant (Variation ID: 289986). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000801965 SCV001453548 pathogenic Lysosomal acid lipase deficiency 2020-09-16 no assertion criteria provided clinical testing

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