Submissions for variant NM_000527.5(LDLR):c.1725C>T (p.Leu575=)

gnomAD frequency: 0.11001  dbSNP: rs1799898

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000238053	SCV000295614	benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
PreventionGenetics, part of Exact Sciences	RCV000247994	SCV000304687	benign	not specified		criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000238053	SCV000322972	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	4 Hmz + 27 Htz / 125 non-FH individuals; MAF = 11,0% in 86 Spanish healthy individuals
Illumina Laboratory Services, Illumina	RCV000238053	SCV000410536	benign	Hypercholesterolemia, familial, 1	2018-01-13	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.
GeneDx	RCV000247994	SCV000513478	benign	not specified	2016-02-17	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	RCV000238053	SCV000689766	benign	Hypercholesterolemia, familial, 1	2017-06-22	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000247994	SCV000711399	benign	not specified	2017-03-15	criteria provided, single submitter	clinical testing	Leu575Leu in exon 12 of LDLR: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 13.8% (1072/8600) of European chromosomes from a broad population by the Exome Aggregation Consortiu m (ExAC, http://exac.broadinstitute.org; dbSNP rs1799898).
Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	RCV000238053	SCV000987022	benign	Hypercholesterolemia, familial, 1	2018-06-11	criteria provided, single submitter	clinical testing	Due to the increased occurrence of the mutation (>= 5%), this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001275780	SCV001725328	benign	Familial hypercholesterolemia	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000238053	SCV001738022	benign	Hypercholesterolemia, familial, 1	2021-06-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002401944	SCV002713682	benign	Cardiovascular phenotype	2016-03-23	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.
GENinCode PLC	RCV001275780	SCV005073994	benign	Familial hypercholesterolemia	2022-07-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004703502	SCV005209379	likely benign	not provided		criteria provided, single submitter	not provided
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000238053	SCV000606499	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Natera, Inc.	RCV001275780	SCV001461315	benign	Familial hypercholesterolemia	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000247994	SCV001924993	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000247994	SCV001963057	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV001275780	SCV003836766	benign	Familial hypercholesterolemia	2023-02-09	no assertion criteria provided	clinical testing