NM_000527.5(LDLR):c.1855T>C (p.Phe619Leu) AND Familial hypercholesterolemia

Clinical significance:Uncertain significance (Last evaluated: Feb 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001182067.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1855T>C (p.Phe619Leu)]

NM_000527.5(LDLR):c.1855T>C (p.Phe619Leu)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.1855T>C (p.Phe619Leu)
Other names:
NP_000518.1:p.F619L; NM_000527.5(LDLR):c.1855T>C
HGVS:
  • NC_000019.10:g.11120101T>C
  • NG_009060.1:g.35721T>C
  • NM_000527.4:c.1855T>C
  • NM_000527.5:c.1855T>CMANE SELECT
  • NM_001195798.2:c.1855T>C
  • NM_001195799.2:c.1732T>C
  • NM_001195800.2:c.1351T>C
  • NM_001195803.2:c.1474T>C
  • NP_000518.1:p.Phe619Leu
  • NP_000518.1:p.Phe619Leu
  • NP_001182727.1:p.Phe619Leu
  • NP_001182728.1:p.Phe578Leu
  • NP_001182729.1:p.Phe451Leu
  • NP_001182732.1:p.Phe492Leu
  • LRG_274t1:c.1855T>C
  • LRG_274:g.35721T>C
  • LRG_274p1:p.Phe619Leu
  • NC_000019.9:g.11230777T>C
  • c.1855T>C
Protein change:
F451L
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000570; dbSNP: rs747134711
NCBI 1000 Genomes Browser:
rs747134711
Molecular consequence:
  • NM_000527.4:c.1855T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.1855T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1855T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1732T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1351T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1474T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001347390Color Health, Inccriteria provided, single submitter
Uncertain significance
(Feb 11, 2020)
germlineclinical testing

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

Description

This missense variant (also known as p.Phe598Leu in the mature protein) replaces phenylalanine with leucine at codon 619 of the LDLR protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in a few individuals affected with familial hypercholesterolemia (PMID: 17094996, 17539906, 20236128, 29720182). This variant has been identified in 1/251492 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.

SCV001347390

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Health, Inc, SCV001347390.1

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

Last Updated: Oct 21, 2021

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