ClinVar Miner

Submissions for variant NM_178172.6(GPIHBP1):c.368G>A (p.Gly123Glu)

gnomAD frequency: 0.00049  dbSNP: rs201685731
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001574958 SCV001801859 uncertain significance not provided 2024-04-11 criteria provided, single submitter clinical testing Identified in patients with hypercholesterolemia and hypertriglyceridemia in published literature (PMID: 33303402, 31153847, 36325899); A published functional study suggests that the p.(G123E) variant at no effect on LPL binding (PMID: 21478160); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31153847, 21478160, 36325899, 33303402)
Labcorp Genetics (formerly Invitae), Labcorp RCV001574958 SCV002406760 benign not provided 2023-12-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343751 SCV002621421 benign Cardiovascular phenotype 2020-09-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
New York Genome Center RCV002468275 SCV002764281 uncertain significance Hyperlipoproteinemia, type 1D 2022-06-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003941025 SCV004761291 uncertain significance GPIHBP1-related disorder 2024-03-21 no assertion criteria provided clinical testing The GPIHBP1 c.368G>A variant is predicted to result in the amino acid substitution p.Gly123Glu. This variant has been reported in an individual with Hypercholesterolemia, although no further evidence was provided to determine its pathogenicity (Gill et al. 2021. PubMed ID: 33303402. Table S2). This variant has also been reported in a cohort study with lipoprotein metabolism or coronary artery disease (Benes et al. 2019. PubMed ID: 31153847). However, functional study showed that this variant did not affect GPIHBP1 expression (Beigneux et al. 2011. PubMed ID: 21478160). This variant is reported in 0.82% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-144297206-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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