Submissions for variant NM_000527.5(LDLR):c.1773C>T (p.Asn591=)

gnomAD frequency: 0.33392  dbSNP: rs688

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000182338	SCV000269224	benign	not specified	2015-12-31	criteria provided, single submitter	clinical testing	p.Asn591Asn in exon 12 of LDLR: This variant is not expected to have clinical si gnificance because it has been identified in 37.8% (45902/121396) of chromosomes tested by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs688).
LDLR-LOVD, British Heart Foundation	RCV000237654	SCV000295647	benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
PreventionGenetics, part of Exact Sciences	RCV000182338	SCV000304688	benign	not specified		criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000237654	SCV000322974	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	19 Hmz + 62 htz / 125 non-FH individuals; MAF = 48,3% in 86 Spanish healthy individuals
Illumina Laboratory Services, Illumina	RCV000237654	SCV000410537	benign	Hypercholesterolemia, familial, 1	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000237654	SCV000689767	benign	Hypercholesterolemia, familial, 1	2017-06-22	criteria provided, single submitter	clinical testing
Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	RCV000237654	SCV000987008	likely benign	Hypercholesterolemia, familial, 1	2018-06-11	criteria provided, single submitter	clinical testing	Due to the increased occurrence of the mutation (>= 5%) and the current estimates of databases (LOVD 3), this variant is classified as likely benign.
Invitae	RCV001275781	SCV001729840	benign	Familial hypercholesterolemia	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000237654	SCV001738023	benign	Hypercholesterolemia, familial, 1	2021-06-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812171	SCV002049915	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV000237654	SCV002503848	benign	Hypercholesterolemia, familial, 1	2023-03-30	criteria provided, single submitter	clinical testing	Population allele frequency is 38% (rs688, 106341/277102 alleles in gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1.
Ambry Genetics	RCV002399653	SCV002714779	benign	Cardiovascular phenotype	2015-12-08	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.
Fulgent Genetics, Fulgent Genetics	RCV000237654	SCV002809584	benign	Hypercholesterolemia, familial, 1	2022-03-25	criteria provided, single submitter	clinical testing
GENinCode PLC	RCV001275781	SCV005073995	benign	Familial hypercholesterolemia	2022-07-14	criteria provided, single submitter	clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000237654	SCV000606510	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Natera, Inc.	RCV001275781	SCV001461318	benign	Familial hypercholesterolemia	2020-09-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000182338	SCV001743237	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000182338	SCV001922080	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000182338	SCV001931172	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV001275781	SCV003836767	benign	Familial hypercholesterolemia	2023-02-09	no assertion criteria provided	clinical testing