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NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 18, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000237644.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr)]

NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr)

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.1576C>A (p.Pro526Thr)
Other names:
NM_000527.5(LDLR):c.1576C>A; p.Pro526Thr
HGVS:
  • NC_000019.10:g.11113752C>A
  • NG_009060.1:g.29372C>A
  • NM_000527.5:c.1576C>AMANE SELECT
  • NM_001195798.2:c.1576C>A
  • NM_001195799.2:c.1453C>A
  • NM_001195800.2:c.1072C>A
  • NM_001195803.2:c.1195C>A
  • NP_000518.1:p.Pro526Thr
  • NP_001182727.1:p.Pro526Thr
  • NP_001182728.1:p.Pro485Thr
  • NP_001182729.1:p.Pro358Thr
  • NP_001182732.1:p.Pro399Thr
  • LRG_274:g.29372C>A
  • NC_000019.9:g.11224428C>A
  • c.1576C>A
Protein change:
P358T
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000213; dbSNP: rs730882106
NCBI 1000 Genomes Browser:
rs730882106
Molecular consequence:
  • NM_000527.5:c.1576C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1576C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1453C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1072C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1195C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypercholesterolemia, familial, 1
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000295504LDLR-LOVD, British Heart Foundation
criteria provided, single submitter

(ACGS Guidelines, 2013)		Likely pathogenic
(Mar 25, 2016) 		germlineliterature only

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

Citation Link,

SCV002568116ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Jan 18, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations.

Chmara M, Wasag B, Zuk M, Kubalska J, Wegrzyn A, Bednarska-Makaruk M, Pronicka E, Wehr H, Defesche JC, Rynkiewicz A, Limon J.

J Appl Genet. 2010;51(1):95-106. doi: 10.1007/BF03195716.

PubMed [citation]
PMID:
20145306

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295504.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV002568116.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr) variant is classified as variant of Uncertain significance for Familial Hypercholesterolemia by applying evidence codes (PM2, PP3 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.951. PP4 - Variant meets PM2. Identified in 1 FH case with clinical diagnosis of probable heterozygous hypercholesterolemia by DLCN score (DLCN = 8) from PMID 32770674.

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

Last Updated: Sep 29, 2024