Submissions for variant NM_000527.5(LDLR):c.2289G>T (p.Glu763Asp)

dbSNP: rs774698247

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000211700	SCV000295931	likely benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Color Diagnostics, LLC DBA Color Health	RCV000776247	SCV000911499	likely benign	Familial hypercholesterolemia	2020-01-23	criteria provided, single submitter	clinical testing
Invitae	RCV000776247	SCV001012665	benign	Familial hypercholesterolemia	2024-01-21	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284645	SCV001470535	likely benign	not provided	2020-08-27	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000211700	SCV001716358	benign	Hypercholesterolemia, familial, 1	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001284645	SCV002504162	likely benign	not provided	2018-07-30	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV004017509	SCV004848151	likely benign	not specified	2017-12-04	criteria provided, single submitter	clinical testing	The p.Glu763Asp variant in LDLR has been reported in 2 individuals with hypercholesterolemia (Hooper 2012, Bangash 2014). This variant has been identified in 0.21% (66/30782) of South Asian chromosomes, including 3 homozygotes, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs774698247) and is reported in ClinVar (Variation ID: 226389). Computational prediction tools and conservation analysis suggest that the p.Glu763Asp variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the p.Glu763Asp variant is likely benign due to its frequency in the general population. ACMG/AMP Criteria applied: PS4_Supporting, BP4, BS1.
Ambry Genetics	RCV004639179	SCV005135985	benign	Cardiovascular phenotype	2024-06-04	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.
Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital	RCV000211700	SCV000268662	uncertain significance	Hypercholesterolemia, familial, 1	2010-04-13	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000776247	SCV002086872	likely benign	Familial hypercholesterolemia	2020-01-31	no assertion criteria provided	clinical testing