ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.709C>T (p.Arg237Trp) (rs148195424)

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Total submissions: 7
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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 RCV000256274 SCV000323052 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research 0/190 non-FH alleles (portuguese normolipidemic individuals); 0/100 normolipidemic individuals
Robarts Research Institute,Western University RCV000256274 SCV000484816 uncertain significance Familial hypercholesterolemia 1 2019-08-22 criteria provided, single submitter clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000417261 SCV000503510 uncertain significance Familial hypercholesterolemia 3 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2, family member = 1 / Software predictions: Damaging
Color RCV000256274 SCV000690989 uncertain significance Familial hypercholesterolemia 1 2017-07-25 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the catalytic peptidase domain in 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 the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals with hypercholesterolemia (PMID 15358785, 16465619, 17765244), as well as in an individual with hypocholesterolemia (PMID 16424354). It has also been identified in 71/118874 chromosomes by the Exome Aggregation Consortium (ExAC) general population database.
Color RCV000771113 SCV000902818 uncertain significance Familial hypercholesterolemia 2018-08-13 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the catalytic peptidase domain in 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 the RNA splicing. Experimental functional study has shown that this variant may cause a moderate increase in the cell surface LDLR levels and LDL internalization (PMID: 16571601). However, clinical significance of this finding is not known. This variant has been reported in individuals with hypercholesterolemia (PMID: 15358785, 16465619, 17765244), as well as in an individual with hypocholesterolemia (PMID: 16424354). This variant has been identified in 188/275458 chromosomes in the general population by the Genome Aggregation Database (gnomAD) and occurs in 0.13% of the Latino population and 0.09% of the non-Finnish European. The relatively high frequency of this variant in the general population suggests that it is unlikely to be disease-causing. However, available evidence is insufficient to conclusively determine the role of this variant in disease.
Invitae RCV000861907 SCV001002323 likely benign not provided 2019-01-29 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000256274 SCV000503554 uncertain significance Familial hypercholesterolemia 1 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing for an unrelated indication. No known history of hyperlipidemia.

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