Submissions for variant NM_174936.4(PCSK9):c.1606G>A (p.Val536Ile)

gnomAD frequency: 0.00001  dbSNP: rs776367625

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523366	SCV000620589	uncertain significance	not provided	2017-09-12	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the PCSK9 gene. The V536I variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 10/7950 (0.13%) alleles from individuals of South Asian ancestry in the Exome Aggregation Consortium (ExAC) dataset (Lek et al., 2016; Exome Variant Server). The V536I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to valine (V) are tolerated across species and where isoleucine (I) is present as the wild type in several species. Finally, in silico analysis predicts this variant likely does not alter the protein structure/function.
Color Diagnostics, LLC DBA Color Health	RCV000775291	SCV000909550	likely benign	Familial hypercholesterolemia	2018-10-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001041471	SCV001205092	likely benign	Hypercholesterolemia, autosomal dominant, 3	2024-08-05	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001041471	SCV004845887	likely benign	Hypercholesterolemia, autosomal dominant, 3	2023-10-30	criteria provided, single submitter	clinical testing