Submissions for variant NM_000527.5(LDLR):c.941-4G>A

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000210248	SCV004022390	benign	Hypercholesterolemia, familial, 1	2023-03-20	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.941-4G>A variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes (BA1, BS2, BP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1 - FAF = 0.02478 (2.478%) in African/African American exomes (gnomAD v2.1.1). BS2 - Case-level data in VCI indicates this variant is identified in heterozygosity in more than 100 non-FH patients from Ambry Genetics. BP4 - No REVEL, splicing evaluation needed. Functional data on splicing not available. A) variant located at -20 to +3 bases from canonical acceptor splice site MES scores: canonical site variant = 7.03; canonical acceptor wt = 7.64. Ratio variant/wt canonical acceptor: 7.03/7.64 = 0.92 ---- It is not above 1.0 B) variant is intronic C) variant is intronic Variant is not predicted to alter splicing.
Cardiovascular Biomarker Research Laboratory, Mayo Clinic	RCV000210248	SCV000266319	uncertain significance	Hypercholesterolemia, familial, 1	2016-08-31	criteria provided, single submitter	research	MAF =<0.3%, likely pathogenic based on the integrative in-silico score
LDLR-LOVD, British Heart Foundation	RCV000210248	SCV000295089	likely benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000210248	SCV000296929	likely benign	Hypercholesterolemia, familial, 1	2015-11-30	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000210248	SCV000484780	likely benign	Hypercholesterolemia, familial, 1	2019-08-22	criteria provided, single submitter	clinical testing
Invitae	RCV000771133	SCV000556777	benign	Familial hypercholesterolemia	2024-01-31	criteria provided, single submitter	clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000210248	SCV000583767	likely pathogenic	Hypercholesterolemia, familial, 1	2017-03-30	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000210248	SCV000588533	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000210248	SCV000743852	benign	Hypercholesterolemia, familial, 1	2017-07-28	criteria provided, single submitter	clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000736080	SCV000864320	likely benign	not specified	2017-05-17	criteria provided, single submitter	clinical testing	BS1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, and is predicted to be tolerated by multiple functional prediction tools.
Color Diagnostics, LLC DBA Color Health	RCV000771133	SCV000902916	benign	Familial hypercholesterolemia	2017-07-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001706207	SCV001469539	benign	not provided	2020-01-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001706207	SCV001949523	benign	not provided	2021-02-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28145427, 23680767, 10422804, 27884173, 26332594, 27765764, 16250003, 27044878)
Ambry Genetics	RCV002372208	SCV002683800	benign	Cardiovascular phenotype	2014-09-29	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001706207	SCV004562333	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV000771133	SCV005045535	benign	Familial hypercholesterolemia		criteria provided, single submitter	clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000210248	SCV000606281	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV001706207	SCV001925595	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000771133	SCV002086398	likely benign	Familial hypercholesterolemia	2019-11-08	no assertion criteria provided	clinical testing