ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.757C>T (p.Leu253Phe)

gnomAD frequency: 0.00098  dbSNP: rs72646508
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082736 SCV000644873 likely benign Hypercholesterolemia, autosomal dominant, 3 2024-02-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589661 SCV000700002 benign not provided 2016-12-15 criteria provided, single submitter clinical testing Variant summary: The PCSK9 c.757C>T (p.Leu253Phe) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant was found in 31/118852 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0030852 (31/10048). This frequency is about 33 times the estimated maximal expected allele frequency of a pathogenic PCSK9 variant (0.0000938), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. Moreover, the variant was reported to be associated with about a 30% reduction of LDL-C levels further supporting a non-disease causing impact. Taken together, this variant is classified as benign.
Color Diagnostics, LLC DBA Color Health RCV000771324 SCV000903591 likely benign Familial hypercholesterolemia 2022-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395411 SCV002672273 benign Cardiovascular phenotype 2022-08-30 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.