NM_000527.5(LDLR):c.815A>C (p.Asn272Thr) AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001179370.4

Allele description [Variation Report for NM_000527.5(LDLR):c.815A>C (p.Asn272Thr)]

NM_000527.5(LDLR):c.815A>C (p.Asn272Thr)

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.815A>C (p.Asn272Thr)

HGVS:

NC_000019.10:g.11106685A>C
NG_009060.1:g.22305A>C
NM_000527.5:c.815A>CMANE SELECT
NM_001195798.2:c.815A>C
NM_001195799.2:c.692A>C
NM_001195800.2:c.314-707A>C
NM_001195803.2:c.434A>C
NP_000518.1:p.Asn272Thr
NP_000518.1:p.Asn272Thr
NP_001182727.1:p.Asn272Thr
NP_001182728.1:p.Asn231Thr
NP_001182732.1:p.Asn145Thr
LRG_274t1:c.815A>C
LRG_274:g.22305A>C
LRG_274p1:p.Asn272Thr
NC_000019.9:g.11217361A>C
NM_000527.4:c.815A>C
NM_000527.5:c.815A>C
c.815A>C

Protein change:

N145T

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001216; dbSNP: rs202213054

NCBI 1000 Genomes Browser:

rs202213054

Molecular consequence:

NM_001195800.2:c.314-707A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.815A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.815A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.692A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.434A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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LOC127548168 [Antechinus flavipes]
LOC127548168 [Antechinus flavipes]
Gene ID:127548168

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001344021	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 15, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21310417, 22698793, 23130880, 28965616, 36325061, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001344021

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 15, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia.

Dušková L, Kopečková L, Jansová E, Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2011 May;216(1):139-45. doi: 10.1016/j.atherosclerosis.2011.01.023. Epub 2011 Jan 21.

PubMed [citation]

PMID:: 21310417

The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations.

Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2012 Aug;223(2):401-8. doi: 10.1016/j.atherosclerosis.2012.05.014. Epub 2012 May 23.

PubMed [citation]

PMID:: 22698793

See all PubMed Citations (6)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001344021.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This missense variant (also known as p.Asn251Thr in the mature protein) replaces asparagine with threonine at codon 272 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 21310417, 22698793, 23130880, 28965616). This variant has also been reported in compound heterozygous state in an individual affected with homozygous familial hypercholesterolemia (PMID: 36325061). This variant has not been identified 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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