ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1473G>T (p.Arg491Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002396991 SCV002701082 uncertain significance Cardiovascular phenotype 2021-12-23 criteria provided, single submitter clinical testing The p.R491S variant (also known as c.1473G>T), located in coding exon 9 of the PCSK9 gene, results from a G to T substitution at nucleotide position 1473. The arginine at codon 491 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003476986 SCV004222368 uncertain significance not provided 2023-04-11 criteria provided, single submitter clinical testing The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/250374 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
All of Us Research Program, National Institutes of Health RCV004007324 SCV004836334 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 491 of the PCSK9 protein. Computational prediction tools indicate that this variant has a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PCSK9-related disorders in the literature. This variant has been identified in 1/250374 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.

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