Submissions for variant NM_000527.5(LDLR):c.2140+5G>A

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000030133	SCV001960942	benign	Hypercholesterolemia, familial, 1	2021-06-18	reviewed by expert panel	curation	NM_000527.5(LDLR):c.2140+5G>A variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes (BA1, BS3_Supporting) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: BA1 - FAF = 0.01030 (1.030%) in European non-Finnish exomes (gnomAD v2.1.1). BS3_supporting - Level 3 assay: PMID:19208450 - study on patient's lymphocytes, Northern blot + real-time PCR + FACS used: normal mRNA processing + 108% low-density lipoprotein receptor activity. ---- functional study is consistent with no damaging effect.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030133	SCV000052788	uncertain	Hypercholesterolemia, familial, 1	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Uncertain significance.
LDLR-LOVD, British Heart Foundation	RCV000030133	SCV000295896	likely benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000030133	SCV000323002	likely benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	19/745 healthy individuals; 1/75 normolipidemic portuguese controls
Cardiovascular Biomarker Research Laboratory, Mayo Clinic	RCV000030133	SCV000323107	likely benign	Hypercholesterolemia, familial, 1	2016-08-31	criteria provided, single submitter	research	MAF =<0.3%
Robarts Research Institute, Western University	RCV000030133	SCV000484792	benign	Hypercholesterolemia, familial, 1	2019-08-22	criteria provided, single submitter	clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000030133	SCV000503470	benign	Hypercholesterolemia, familial, 1	2016-12-16	criteria provided, single submitter	clinical testing	subject mutated among 2600 FH index cases screened = 1/Polymorphisme cf whitall et al J Med Genet, 2002
Labcorp Genetics (formerly Invitae), Labcorp	RCV000771073	SCV000556791	benign	Familial hypercholesterolemia	2025-02-02	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000030133	SCV000588636	likely benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000030133	SCV000607680	likely benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV000030133	SCV000689773	likely benign	Hypercholesterolemia, familial, 1	2017-06-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000614028	SCV000728650	benign	not specified	2017-06-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000771073	SCV000902603	benign	Familial hypercholesterolemia	2018-06-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000858033	SCV001134260	benign	not provided	2022-12-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000030133	SCV001286051	benign	Hypercholesterolemia, familial, 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000858033	SCV002546066	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	LDLR: BS1, BS2
Ambry Genetics	RCV002426525	SCV002730269	benign	Cardiovascular phenotype	2021-11-18	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	RCV000858033	SCV004563880	benign	not provided	2024-11-19	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV000771073	SCV005050215	benign	Familial hypercholesterolemia	2022-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000858033	SCV005312109	benign	not provided		criteria provided, single submitter	not provided
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000030133	SCV000606609	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000030133	SCV000733830	likely benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000614028	SCV001919354	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000858033	SCV001970991	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003904871	SCV004732085	likely benign	LDLR-related disorder	2023-11-30	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).