ClinVar Miner

Submissions for variant NM_000236.3(LIPC):c.866C>T (p.Ser289Phe)

gnomAD frequency: 0.00076  dbSNP: rs121912502
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000015537 SCV000245631 uncertain significance Hyperlipidemia due to hepatic triglyceride lipase deficiency 2014-10-16 criteria provided, single submitter clinical testing The p.Ser289Phe variant in LIPC has been reported in 1 compound heterozygous individual with hepatic lipase deficiency and segregated with disease in 3 affected compound heterozygous relatives from 1 family (Hegele 1991). This variant has been identified in 0.13% (11/8584) of European American chromosomes and 0.05% (4/4384) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs121912502). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. In vitro assays indicate the p.Ser289Phe variant leads to reduced LIPC activity (Durstenfeld 1994). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analysis also suggest that the p.Ser289Phe variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Ser289Phe variant is uncertain.
Illumina Laboratory Services, Illumina RCV000015537 SCV001276202 uncertain significance Hyperlipidemia due to hepatic triglyceride lipase deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV002054443 SCV002483323 likely benign not provided 2023-07-27 criteria provided, single submitter clinical testing
OMIM RCV000015537 SCV000035802 pathogenic Hyperlipidemia due to hepatic triglyceride lipase deficiency 1991-08-30 no assertion criteria provided literature only

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