ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1430G>A (p.Cys477Tyr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV004529260 SCV004112279 uncertain significance PCSK9-related disorder 2023-04-20 criteria provided, single submitter clinical testing The PCSK9 c.1430G>A variant is predicted to result in the amino acid substitution p.Cys477Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. 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 RCV004011303 SCV004832877 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2023-04-10 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 477 of the PCSK9 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). 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 not been identified 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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