ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.1487G>A (p.Arg496Gln) (rs139669564)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505200 SCV000599433 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter curation
Integrated Genetics/Laboratory Corporation of America RCV000780579 SCV000917975 benign not specified 2017-09-25 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.1487G>A (p.Arg496Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). One functional study showed that this variant was associated with amounts of cell surface LDLR and LDL internalized that were comparable to that of wild-type levels (Cameron_2006). The variant was found in the control population dataset of gnomAD in 68/240046 control chromosomes at a frequency of 0.0002833, which is approximately 14 times the estimated maximal expected allele frequency of a pathogenic PCSK9 variant (0.00002), suggesting this variant is likely a benign polymorphism. One study found this variant in a subject homozygous for apolipoprotein E-2 who presented with Type III hyperlipoproteinaemia, without strong evidence for causality. This variant was found co-occurring with the pathogenic LDLR c.1775G>A, p.Gly592Glu mutation in an internal specimen, supporting a benign impact of the variant. One clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, this variant is classified as benign.
Invitae RCV000525584 SCV000644862 likely benign Hypercholesterolemia, autosomal dominant, 3 2017-10-22 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000505200 SCV000606712 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Robarts Research Institute,Western University RCV000505200 SCV000782978 uncertain significance Familial hypercholesterolemia 2018-01-02 criteria provided, single submitter clinical testing

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