NM_000527.5(LDLR):c.626G>A (p.Cys209Tyr) AND Familial hypercholesterolemia

Clinical significance:Likely pathogenic (Last evaluated: Aug 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001523918.1

Allele description [Variation Report for NM_000527.5(LDLR):c.626G>A (p.Cys209Tyr)]

NM_000527.5(LDLR):c.626G>A (p.Cys209Tyr)

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.626G>A (p.Cys209Tyr)
HGVS:
  • NC_000019.10:g.11105532G>A
  • NG_009060.1:g.21152G>A
  • NM_000527.4:c.626G>A
  • NM_000527.5:c.626G>AMANE SELECT
  • NM_001195798.2:c.626G>A
  • NM_001195799.2:c.503G>A
  • NM_001195800.2:c.314-1860G>A
  • NM_001195803.2:c.314-1033G>A
  • NP_000518.1:p.Cys209Tyr
  • NP_000518.1:p.Cys209Tyr
  • NP_001182727.1:p.Cys209Tyr
  • NP_001182728.1:p.Cys168Tyr
  • LRG_274t1:c.626G>A
  • LRG_274:g.21152G>A
  • LRG_274p1:p.Cys209Tyr
  • NC_000019.9:g.11216208G>A
  • c.626G>A
Protein change:
C168Y
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000920; dbSNP: rs879254600
NCBI 1000 Genomes Browser:
rs879254600
Molecular consequence:
  • NM_001195800.2:c.314-1860G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1033G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.4:c.626G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.626G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.626G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.503G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001733655Color Health, Inccriteria provided, single submitter
Likely pathogenic
(Aug 6, 2020)
germlineclinical testing

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

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, SCV001733655.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This missense variant (also known as p.Cys188Tyr in the mature protein) replaces cysteine with tyrosine at codon 209 in the LDLR type A repeat 5 of the LDLR protein. This variant alters a conserved cysteine residue that is critical for proper protein folding and function (PMID: 2088165, 6091915, 15952897). Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 20 individuals affected with familial hypercholesterolemia (PMID: 11754108, 21310417, 22698793, 27824480, 28502495, 29396260). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 19, 2021

Support Center