Submissions for variant NM_000527.5(LDLR):c.1061-8T>C

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000030123	SCV002506403	benign	Hypercholesterolemia, familial, 1	2022-03-25	reviewed by expert panel	curation	The NM_000527.5 (LDLR):c.1061-8T>C 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/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1: PopMax FAF = 0.008564 in African/African American population in gnomAD (gnomAD v2.2.1). BS3_Supporting: Heterozygous patient cells were used for RNA assays (Level 3 experiment) shown normal LDLR transcripts reported from 2 research labs: Bourbon et al, Unidade de Investigacao Cardiovascular, Instituto Nacional de Saude Dr. Ricardo Jorge, Lisboa, Portugal, (PMID 19411563); Holla et al, Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway, (PMID 19208450). Functional studies is consistent with no damaging effect.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030123	SCV000052778	uncertain	Hypercholesterolemia, familial, 1	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Uncertain significance.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000030123	SCV000257699	likely benign	Hypercholesterolemia, familial, 1	2015-06-17	criteria provided, single submitter	clinical testing
LDLR-LOVD, British Heart Foundation	RCV000030123	SCV000295183	benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
PreventionGenetics, part of Exact Sciences	RCV000245346	SCV000304681	benign	not specified		criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000030123	SCV000322930	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	2/75 Portuguese normolipidemic individuals
Cardiovascular Biomarker Research Laboratory, Mayo Clinic	RCV000030123	SCV000323106	likely benign	Hypercholesterolemia, familial, 1	2016-08-31	criteria provided, single submitter	research	MAF =<0.3%
Robarts Research Institute, Western University	RCV000030123	SCV000484782	benign	Hypercholesterolemia, familial, 1	2019-08-22	criteria provided, single submitter	clinical testing
Invitae	RCV001083488	SCV000556781	benign	Familial hypercholesterolemia	2024-02-01	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000030123	SCV000588550	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000030123	SCV000607555	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV001083488	SCV000689757	benign	Familial hypercholesterolemia	2022-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000245346	SCV000730509	benign	not specified	2017-05-11	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759074	SCV000888160	benign	not provided	2022-07-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000759074	SCV001151657	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	LDLR: BP4, BS2
Illumina Laboratory Services, Illumina	RCV000030123	SCV001286365	benign	Hypercholesterolemia, familial, 1	2018-02-12	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000759074	SCV002048406	benign	not provided	2023-06-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399342	SCV002714544	benign	Cardiovascular phenotype	2018-12-19	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000030123	SCV000606310	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000030123	SCV000733818	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000030123	SCV001190847	benign	Hypercholesterolemia, familial, 1	2020-02-05	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000245346	SCV001919776	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000245346	SCV001963930	benign	not specified		no assertion criteria provided	clinical testing