ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2411T>C (p.Leu804Pro)

gnomAD frequency: 0.00002  dbSNP: rs879255203
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238240 SCV000295998 uncertain significance Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Color Diagnostics, LLC DBA Color Health RCV001182070 SCV001347394 uncertain significance Familial hypercholesterolemia 2019-07-30 criteria provided, single submitter clinical testing This missense variant (also known as p.Leu783Pro in the mature protein) replaces leucine with proline at codon 804 of the LDLR protein. Computational prediction tools and conservation analyses suggest that this variant may not impact protein function. Of note, leucine at this position is poorly conserved in mammals, suggesting that other amino acids may be tolerated for function. Computational splicing tools suggest that this variant may not impact RNA splicing. A functional study has shown that this variant may partially affect integration of the LDLR protein in the cell membrane (PMID: 26220972). However, clinical relevance of this observation is not known. This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 16250003). This variant has been identified in 1/31392 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001582802 SCV001821225 uncertain significance not specified 2021-08-12 criteria provided, single submitter clinical testing Variant summary: LDLR c.2411T>C (p.Leu804Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251326 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2411T>C has been reported in the literature in an individual affected with Familial Hypercholesterolemia (Fouchier_2005). This report does not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. One functional study has reported the variant to cause defective gamma-secretase cleavage, but otherwise appears to be similar to the WT-LDLR. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000238240 SCV002791786 uncertain significance Hypercholesterolemia, familial, 1 2021-09-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000238240 SCV004820682 uncertain significance Hypercholesterolemia, familial, 1 2023-11-30 criteria provided, single submitter clinical testing This missense variant (also known as p.Leu783Pro in the mature protein) replaces leucine with proline at codon 804 of the LDLR protein. Computational prediction tools and conservation analyses suggest that this variant may not impact protein function. Of note, leucine at this position is poorly conserved in mammals, suggesting that other amino acids may be tolerated for function. Computational splicing tools suggest that this variant may not impact RNA splicing. A functional study has shown that this variant may partially affect integration of the LDLR protein in the cell membrane (PMID: 26220972). However, clinical relevance of this observation is not known. This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 16250003). This variant has been identified in 1/31392 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238240 SCV000606646 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research
Natera, Inc. RCV001182070 SCV002086879 uncertain significance Familial hypercholesterolemia 2020-02-20 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.