NM_000527.5(LDLR):c.2506G>A (p.Val836Ile) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 20, 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:: RCV002429178.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2506G>A (p.Val836Ile)]

NM_000527.5(LDLR):c.2506G>A (p.Val836Ile)

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.2506G>A (p.Val836Ile)

HGVS:

NC_000019.10:g.11129629G>A
NG_009060.1:g.45249G>A
NM_000527.5:c.2506G>AMANE SELECT
NM_001195798.2:c.2506G>A
NM_001195799.2:c.2383G>A
NM_001195800.2:c.2002G>A
NM_001195803.2:c.1972G>A
NP_000518.1:p.Val836Ile
NP_000518.1:p.Val836Ile
NP_001182727.1:p.Val836Ile
NP_001182728.1:p.Val795Ile
NP_001182729.1:p.Val668Ile
NP_001182732.1:p.Val658Ile
LRG_274t1:c.2506G>A
LRG_274:g.45249G>A
LRG_274p1:p.Val836Ile
NC_000019.9:g.11240305G>A
NM_000527.4:c.2506G>A
c.2506G>A

Protein change:

V658I

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001089; dbSNP: rs879255220

NCBI 1000 Genomes Browser:

rs879255220

Molecular consequence:

NM_000527.5:c.2506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.2383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.2002G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1972G>A - 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
SCV002742365	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16250003, 18325082 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002742365

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 20, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Update of the molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Kastelein JJ, Defesche JC.

Hum Mutat. 2005 Dec;26(6):550-6.

PubMed [citation]

PMID:: 16250003

Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database.

Leigh SE, Foster AH, Whittall RA, Hubbart CS, Humphries SE.

Ann Hum Genet. 2008 Jul;72(Pt 4):485-98. doi: 10.1111/j.1469-1809.2008.00436.x. Epub 2008 Mar 5.

PubMed [citation]

PMID:: 18325082

Details of each submission

From Ambry Genetics, SCV002742365.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.V836I variant (also known as c.2506G>A), located in coding exon 17 of the LDLR gene, results from a G to A substitution at nucleotide position 2506. The valine at codon 836 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Fouchier SW et al. Hum. Mutat., 2005 Dec;26:550-6; Leigh SE et al. Ann. Hum. Genet., 2008 Jul;72:485-98). 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 7, 2024

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