ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1503G>A (p.Glu501=)

gnomAD frequency: 0.00001  dbSNP: rs986151799
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001175681 SCV001339372 uncertain significance Familial hypercholesterolemia 2021-05-19 criteria provided, single submitter clinical testing This variant changes the last nucleotide G of exon 5 to A in the PCSK9 gene. Computational splicing tools suggest that this variant may impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 2/271364 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002490860 SCV002775813 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2021-10-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004527615 SCV004104918 uncertain significance PCSK9-related disorder 2023-07-31 criteria provided, single submitter clinical testing The PCSK9 c.1503G>A variant is not predicted to result in an amino acid change (p.=). However, this variant is predicted to affect splicing (Alamut Visual Plus v1.6.1). This variant has reported in a study of patients with hypercholesterolemia (Huijgen et al. 2012. PubMed ID: 22095935). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-55524320-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV002490860 SCV004844971 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2023-11-30 criteria provided, single submitter clinical testing This variant changes the last nucleotide G of exon 5 to A in the PCSK9 gene. Computational splicing tools suggest that this variant may impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 2/271364 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000508771 SCV000606713 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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