NM_000527.5(LDLR):c.1733T>C (p.Val578Ala) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 25, 2021
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:: RCV002404297.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1733T>C (p.Val578Ala)]

NM_000527.5(LDLR):c.1733T>C (p.Val578Ala)

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.1733T>C (p.Val578Ala)

HGVS:

NC_000019.10:g.11116886T>C
NG_009060.1:g.32506T>C
NM_000527.5:c.1733T>CMANE SELECT
NM_001195798.2:c.1733T>C
NM_001195799.2:c.1610T>C
NM_001195800.2:c.1229T>C
NM_001195803.2:c.1352T>C
NP_000518.1:p.Val578Ala
NP_000518.1:p.Val578Ala
NP_001182727.1:p.Val578Ala
NP_001182728.1:p.Val537Ala
NP_001182729.1:p.Val410Ala
NP_001182732.1:p.Val451Ala
LRG_274t1:c.1733T>C
LRG_274:g.32506T>C
LRG_274p1:p.Val578Ala
NC_000019.9:g.11227562T>C
NM_000527.4:c.1733T>C

Protein change:

V410A

Links:

dbSNP: rs72658864

NCBI 1000 Genomes Browser:

rs72658864

Molecular consequence:

NM_000527.5:c.1733T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1733T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1610T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1352T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Opisthocomus hoazin
Opisthocomus hoazin
Opisthocomus hoazin RefSeq Genome sequencing

BioProject
Hap1 huntingtin-associated protein 1 [Mus musculus]
Hap1 huntingtin-associated protein 1 [Mus musculus]
Gene ID:15114

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002713888	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 25, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21829380, 25740221, 26366554 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002713888

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 25, 2021)

germline

clinical testing

PubMed (3)
[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

Fine mapping of five loci associated with low-density lipoprotein cholesterol detects variants that double the explained heritability.

Sanna S, Li B, Mulas A, Sidore C, Kang HM, Jackson AU, Piras MG, Usala G, Maninchedda G, Sassu A, Serra F, Palmas MA, Wood WH 3rd, Njølstad I, Laakso M, Hveem K, Tuomilehto J, Lakka TA, Rauramaa R, Boehnke M, Cucca F, Uda M, et al.

PLoS Genet. 2011 Jul;7(7):e1002198. doi: 10.1371/journal.pgen.1002198. Epub 2011 Jul 28.

PubMed [citation]

PMID:: 21829380
PMCID:: PMC3145627

Methods for association analysis and meta-analysis of rare variants in families.

Feng S, Pistis G, Zhang H, Zawistowski M, Mulas A, Zoledziewska M, Holmen OL, Busonero F, Sanna S, Hveem K, Willer C, Cucca F, Liu DJ, Abecasis GR.

Genet Epidemiol. 2015 May;39(4):227-38. doi: 10.1002/gepi.21892. Epub 2015 Mar 4.

PubMed [citation]

PMID:: 25740221
PMCID:: PMC4459524

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002713888.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.V578A variant (also known as c.1733T>C), located in coding exon 12 of the LDLR gene, results from a T to C substitution at nucleotide position 1733. The valine at codon 578 is replaced by alanine, an amino acid with similar properties. In genome-wide association studies (GWAS) performed in a Sardinian population, this variant has been suggested to have some association with dyslipidemia risks (Sanna S et al. PLoS Genet, 2011 Jul;7:e1002198; Sidore C et al. Nat Genet, 2015 Nov;47:1272-1281). This amino acid position is highly 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: Jun 23, 2024

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