NM_000527.5(LDLR):c.2034G>T (p.Gln678His) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 23, 2022
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:: RCV002419830.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2034G>T (p.Gln678His)]

NM_000527.5(LDLR):c.2034G>T (p.Gln678His)

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.2034G>T (p.Gln678His)

HGVS:

NC_000019.10:g.11120416G>T
NG_009060.1:g.36036G>T
NM_000527.5:c.2034G>TMANE SELECT
NM_001195798.2:c.2034G>T
NM_001195799.2:c.1911G>T
NM_001195800.2:c.1530G>T
NM_001195803.2:c.1606+183G>T
NP_000518.1:p.Gln678His
NP_000518.1:p.Gln678His
NP_001182727.1:p.Gln678His
NP_001182728.1:p.Gln637His
NP_001182729.1:p.Gln510His
LRG_274t1:c.2034G>T
LRG_274:g.36036G>T
LRG_274p1:p.Gln678His
NC_000019.9:g.11231092G>T
NM_000527.4:c.2034G>T

Protein change:

Q510H

Molecular consequence:

NM_001195803.2:c.1606+183G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.2034G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2034G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1911G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1530G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002723005	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002723005

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 23, 2022)

germline

clinical testing

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

Citation Link

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

Molecular genetic testing for autosomal dominant hypercholesterolemia in 29,449 Norwegian index patients and 14,230 relatives during the years 1993-2020.

Leren TP, Bogsrud MP.

Atherosclerosis. 2021 Apr;322:61-66. doi: 10.1016/j.atherosclerosis.2021.02.022. Epub 2021 Feb 23.

PubMed [citation]

PMID:: 33740630

Details of each submission

From Ambry Genetics, SCV002723005.2

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

Description

The p.Q678H variant (also known as c.2034G>T), located in coding exon 14 of the LDLR gene, results from a G to T substitution at nucleotide position 2034. The glutamine at codon 678 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a familial hypercholesterolemia (FH) genetic testing cohort; however, clinical details were limited (Leren TP et al. Atherosclerosis, 2021 04;322:61-66). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 1, 2024

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