ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2343G>T (p.Glu781Asp)

gnomAD frequency: 0.00001  dbSNP: rs761683856
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237385 SCV000295959 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Robarts Research Institute, Western University RCV000237385 SCV000484720 uncertain significance Hypercholesterolemia, familial, 1 2019-08-22 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000237385 SCV001422787 uncertain significance Hypercholesterolemia, familial, 1 2020-01-22 criteria provided, single submitter curation The p.Glu781Asp (sometimes called p.Glu760Asp) variant in LDLR has been reported in at least 1 Portuguese individual with Familial Hypercholesterolemia (PMID: 11668627, 27765764), and has been identified in 0.005782% (2/34592) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs761683856). 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 as a likely benign and a likely pathogenic variant in ClinVar (Variation ID: 252290). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Glu781Asp variant is uncertain. ACMG/AMP Criteria applied: none (Richards 2015).
Color Diagnostics, LLC DBA Color Health RCV001524620 SCV001734546 uncertain significance Familial hypercholesterolemia 2020-11-04 criteria provided, single submitter clinical testing This missense variant (also known as p.Glu760Asp in the mature protein) replaces glutamic acid with aspartic acid at codon 781 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with familial hypercholesterolemia (PMID: 11668627, 27765764). This variant has been identified in 2/251460 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV000237385 SCV005427658 uncertain significance Hypercholesterolemia, familial, 1 2024-05-09 criteria provided, single submitter clinical testing This missense variant (also known as p.Glu760Asp in the mature protein) replaces glutamic acid with aspartic acid at codon 781 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with familial hypercholesterolemia (PMID: 11668627, 27765764). This variant has been identified in 2/251460 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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