Submissions for variant NM_174936.4(PCSK9):c.522C>T (p.Pro174=)

dbSNP: rs373018373

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001191336	SCV001359113	likely benign	Familial hypercholesterolemia	2018-07-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001859151	SCV002245049	uncertain significance	Hypercholesterolemia, autosomal dominant, 3	2021-09-17	criteria provided, single submitter	clinical testing	This sequence change affects codon 174 of the PCSK9 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PCSK9 protein. This variant is present in population databases (rs373018373, ExAC 0.009%). This variant has not been reported in the literature in individuals with PCSK9-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV003163479	SCV003858520	likely benign	Cardiovascular phenotype	2023-01-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen	RCV003311958	SCV004009847	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	PCSK9: BP4, BP7
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331073	SCV004038261	uncertain significance	not specified	2023-08-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003311958	SCV004222381	benign	not provided	2023-04-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001859151	SCV004840369	likely benign	Hypercholesterolemia, autosomal dominant, 3	2023-12-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004538425	SCV004754151	likely benign	PCSK9-related disorder	2019-06-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).