ClinVar Miner

Submissions for variant NM_000236.3(LIPC):c.738_739dup (p.Gly247fs)

gnomAD frequency: 0.00023  dbSNP: rs749932377
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778444 SCV000914690 uncertain significance Hyperlipidemia due to hepatic triglyceride lipase deficiency 2018-10-25 criteria provided, single submitter clinical testing The LIPC c.738_739dupCG (p.Gly247AlafsTer12) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. Based on this search no publications were found reporting the p.Gly247AlafsTer12 in association with hepatic lipase deficiency, however the p.Gly247AlafsTer12 variant was reported in one study in a 19 year old female with mixed hyperlipidemia, in a heterozygous state (Buonuomo et al. 2017). The p.Gly247AlafsTer12 variant is reported at a frequency of 0.000537 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence and the potential impact of frameshift variants, the p.Gly247AlafsTer12 variant is classified as a variant of unknown significance but suspicious for pathogenicity for hepatic lipase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV001873173 SCV002219828 uncertain significance not provided 2024-07-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly247Alafs*12) in the LIPC gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LIPC cause disease. This variant is present in population databases (rs749932377, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with dyslipidemia, hyperlipidemia, and/or reduced HDL cholesterol levels (PMID: 28951076, 33339817, 34662886, 36325899). ClinVar contains an entry for this variant (Variation ID: 631739). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
New York Genome Center RCV000778444 SCV002764282 uncertain significance Hyperlipidemia due to hepatic triglyceride lipase deficiency 2021-05-07 criteria provided, single submitter clinical testing

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