ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.412C>T (p.Pro138Ser)

dbSNP: rs780564433
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000689522 SCV000817176 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 138 of the PCSK9 protein (p.Pro138Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs780564433, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with PCSK9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001185725 SCV001351978 uncertain significance Familial hypercholesterolemia 2022-12-13 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 138 of the PCSK9 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 1/251488 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.
Fulgent Genetics, Fulgent Genetics RCV000689522 SCV002786110 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2021-09-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000689522 SCV004842147 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2024-03-24 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 138 of the PCSK9 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 1/251488 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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