Submissions for variant NM_174936.4(PCSK9):c.45GCT[10] (p.Leu21_Leu23dup)

dbSNP: rs35574083

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000733477	SCV000861553	uncertain significance	not provided	2018-06-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781700	SCV000919963	likely benign	not specified	2018-01-03	criteria provided, single submitter	clinical testing	Variant summary: The c.57_65dupGCTGCTGCT (p.Leu19_Leu21dup) in PCSK9 gene leads to an in-frame insertion of three leucines to the stretch of 9 leucines in exon 1 of PCSK9. This variant was found in 36/185508 control chromosomes at a frequency of 0.0001941, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic PCSK9 variant (0.0000938), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals, nor has it been cited by any reputable databases/clinical laboratories. Addition of one or two leucines to poly Leu stretch are believed to be associated with lower LDL-cholesterol levels in general populations (Abifadel_2009; Slimani_2012). Additional population and clinical data needed to classify the variant with confidence. Taken together, this variant is classified as likely benign.
Invitae	RCV001081621	SCV001004509	likely benign	Hypercholesterolemia, autosomal dominant, 3	2024-01-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001189676	SCV001357016	likely benign	Familial hypercholesterolemia	2018-12-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000733477	SCV001818106	likely benign	not provided	2022-10-21	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000733477	SCV002046856	benign	not provided	2021-04-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000781700	SCV002518452	benign	not specified	2023-08-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002343605	SCV002650573	likely benign	Cardiovascular phenotype	2021-02-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.