Submissions for variant NM_000527.5(LDLR):c.165C>G (p.Gly55=)

gnomAD frequency: 0.00015  dbSNP: rs150644181

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Robarts Research Institute, Western University	RCV000408777	SCV000484772	benign	Hypercholesterolemia, familial, 1	2019-08-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000866978	SCV001008155	likely benign	Familial hypercholesterolemia	2025-01-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000866978	SCV001346456	likely benign	Familial hypercholesterolemia	2017-09-01	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000408777	SCV001422914	likely benign	Hypercholesterolemia, familial, 1	2020-01-22	criteria provided, single submitter	curation	The c.165C>G variant in LDLR has been reported in 1 individual with Familial Hypercholesterolemia in ClinVar (Variation ID: 369857), and has been identified in 0.05211% (13/24946) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs150644181). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. This variant has also been reported likely pathogenic and benign in ClinVar (Variation ID: 369857). Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BP4, BP7 (Richards 2015).
Ambry Genetics	RCV002402096	SCV002707179	likely benign	Cardiovascular phenotype	2023-06-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000408777	SCV002809044	likely benign	Hypercholesterolemia, familial, 1	2021-10-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003114522	SCV003800385	likely benign	not provided	2022-09-14	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003114522	SCV004219955	likely benign	not provided	2023-04-24	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000408777	SCV004820124	likely benign	Hypercholesterolemia, familial, 1	2023-12-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004701453	SCV005202424	likely benign	not specified	2024-07-27	criteria provided, single submitter	clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000408777	SCV000606029	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV003970088	SCV004785705	likely benign	LDLR-related disorder	2022-08-07	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).