NM_000527.5(LDLR):c.406G>A (p.Asp136Asn) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 25, 2020
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:: RCV002320411.2

Allele description [Variation Report for NM_000527.5(LDLR):c.406G>A (p.Asp136Asn)]

NM_000527.5(LDLR):c.406G>A (p.Asp136Asn)

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.406G>A (p.Asp136Asn)

HGVS:

NC_000019.10:g.11105312G>A
NG_009060.1:g.20932G>A
NM_000527.5:c.406G>AMANE SELECT
NM_001195798.2:c.406G>A
NM_001195799.2:c.283G>A
NM_001195800.2:c.314-2080G>A
NM_001195803.2:c.314-1253G>A
NP_000518.1:p.Asp136Asn
NP_001182727.1:p.Asp136Asn
NP_001182728.1:p.Asp95Asn
LRG_274t1:c.406G>A
LRG_274:g.20932G>A
NC_000019.9:g.11215988G>A
NM_000527.4:c.406G>A

Protein change:

D136N

Links:

dbSNP: rs2077270167

NCBI 1000 Genomes Browser:

rs2077270167

Molecular consequence:

NM_001195800.2:c.314-2080G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1253G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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SLC35D3 [Pan paniscus]
SLC35D3 [Pan paniscus]
Gene ID:100992476

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002631380	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 25, 2020)	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

SCV002631380

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 25, 2020)

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

Evaluation of high-resolution melting analysis for screening the LDL receptor gene.

Laurie AD, George PM.

Clin Biochem. 2009 Apr;42(6):528-35. doi: 10.1016/j.clinbiochem.2008.11.015. Epub 2008 Dec 11.

PubMed [citation]

PMID:: 19118540

Details of each submission

From Ambry Genetics, SCV002631380.2

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

Description

The p.D136N variant (also known as c.406G>A), located in coding exon 4 of the LDLR gene, results from a G to A substitution at nucleotide position 406. The aspartic acid at codon 136 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in the literature (as c.406G>A p.D115N), however clinical details were not provided (Laurie AD et al. Clin. Biochem., 2009 Apr;42:528-35). Additionally, this alteration impacts a residue in the conserved cluster of acidic amino acids at the C-terminal end of LDLR class A repeat 3 (Jeon H and Blacklow C. Annu. Rev. Biochem. 2005;74:535-62). 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: Sep 1, 2024

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