NM_000527.5(LDLR):c.2411T>C (p.Leu804Pro) AND Familial hypercholesterolemia

Clinical significance:Uncertain significance (Last evaluated: Jul 30, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000527.5(LDLR):c.2411T>C (p.Leu804Pro)]

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

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.2411T>C (p.Leu804Pro)
  • NC_000019.10:g.11129534T>C
  • NG_009060.1:g.45154T>C
  • NM_000527.4:c.2411T>C
  • NM_000527.5:c.2411T>CMANE SELECT
  • NM_001195798.2:c.2411T>C
  • NM_001195799.2:c.2288T>C
  • NM_001195800.2:c.1907T>C
  • NM_001195803.2:c.1877T>C
  • NP_000518.1:p.Leu804Pro
  • NP_000518.1:p.Leu804Pro
  • NP_001182727.1:p.Leu804Pro
  • NP_001182728.1:p.Leu763Pro
  • NP_001182729.1:p.Leu636Pro
  • NP_001182732.1:p.Leu626Pro
  • LRG_274t1:c.2411T>C
  • LRG_274:g.45154T>C
  • LRG_274p1:p.Leu804Pro
  • NC_000019.9:g.11240210T>C
  • c.2411T>C
Protein change:
LDLR-LOVD, British Heart Foundation: LDLR_001087; dbSNP: rs879255203
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000527.4:c.2411T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.2411T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.2411T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.2288T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1907T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1877T>C - missense variant - [Sequence Ontology: SO:0001583]


Familial hypercholesterolemia (FH)
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001347394Color Health, Inccriteria provided, single submitter
Uncertain significance
(Jul 30, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]


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.


Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod



Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From Color Health, Inc, SCV001347394.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 6, 2021

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