ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.2044C>T (p.Arg682Trp)

gnomAD frequency: 0.00004  dbSNP: rs753308448
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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 RCV001190138 SCV001357557 uncertain significance Familial hypercholesterolemia 2023-12-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the CM3 domain of the PCSK9 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not 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 5/242858 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Ambry Genetics RCV002418642 SCV002721746 uncertain significance Cardiovascular phenotype 2021-09-17 criteria provided, single submitter clinical testing The p.R682W variant (also known as c.2044C>T), located in coding exon 12 of the PCSK9 gene, results from a C to T substitution at nucleotide position 2044. The arginine at codon 682 is replaced by tryptophan, 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.
Breakthrough Genomics, Breakthrough Genomics RCV004691383 SCV005186716 uncertain significance not provided criteria provided, single submitter not provided

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