ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1250A>G (p.His417Arg)

gnomAD frequency: 0.00002  dbSNP: rs769163891
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181291 SCV001346402 uncertain significance Familial hypercholesterolemia 2019-10-08 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 417 of the PCSK9 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 5/251242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.
All of Us Research Program, National Institutes of Health RCV004006732 SCV004836675 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 417 of the PCSK9 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 5/251242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004690003 SCV005185256 uncertain significance not specified 2024-05-20 criteria provided, single submitter clinical testing

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