ClinVar Miner

Submissions for variant NM_000237.3(LPL):c.242G>A (p.Gly81Asp)

dbSNP: rs762007406
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV001823501 SCV002072984 likely pathogenic Hyperlipoproteinemia, type I criteria provided, single submitter clinical testing The missense variant p.G81D in LPL (NM_000237.3) has been reported previously as a pathogenic variant in patients with severe hyperchylomicronemia (Stefanutti et al., 2013; Hegele et al., 2018). The missense variant c.242G>A (p.G81D) in LPL (NM_000237.3) is observed in 1/113558 (0.0009%) alleles from individuals of European (Non-Finnish) background in the gnomAD dataset (Exome Aggregation Consortium et al., 2016), but was not seen in the homozygous state. The p.G81D missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 81 of LPL is conserved in all mammalian species. The nucleotide c.242 in LPL is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic
Mendelics RCV002246536 SCV002517573 pathogenic Hyperlipidemia, familial combined, LPL related 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV003299025 SCV003997137 likely pathogenic Cardiovascular phenotype 2023-05-23 criteria provided, single submitter clinical testing The p.G81D variant (also known as c.242G>A), located in coding exon 2 of the LPL gene, results from a G to A substitution at nucleotide position 242. The glycine at codon 81 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been reported as homozygous and as a compound heterozygote in subjects with features consistent with chylomicronemia syndrome (Stefanutti C et al. Atheroscler Suppl, 2013 Jan;14:73-6; Rabacchi C et al. Atherosclerosis, 2015 Jul;241:79-86; Hegele RA et al. J Clin Lipidol, 2018 Apr;12:920-927.e4). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 majority of available evidence to date, this variant is likely to be pathogenic.

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