NM_000527.5(LDLR):c.988A>G (p.Asn330Asp) AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 28, 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:: RCV001524025.2

Allele description [Variation Report for NM_000527.5(LDLR):c.988A>G (p.Asn330Asp)]

NM_000527.5(LDLR):c.988A>G (p.Asn330Asp)

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.988A>G (p.Asn330Asp)

HGVS:

NC_000019.10:g.11110699A>G
NG_009060.1:g.26319A>G
NM_000527.5:c.988A>GMANE SELECT
NM_001195798.2:c.988A>G
NM_001195799.2:c.865A>G
NM_001195800.2:c.484A>G
NM_001195803.2:c.607A>G
NP_000518.1:p.Asn330Asp
NP_001182727.1:p.Asn330Asp
NP_001182728.1:p.Asn289Asp
NP_001182729.1:p.Asn162Asp
NP_001182732.1:p.Asn203Asp
LRG_274t1:c.988A>G
LRG_274:g.26319A>G
NC_000019.9:g.11221375A>G
NM_000527.4:c.988A>G

Protein change:

N162D

Links:

dbSNP: rs730882095

NCBI 1000 Genomes Browser:

rs730882095

Molecular consequence:

NM_000527.5:c.988A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.988A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.865A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.484A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.607A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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PREDICTED: Mus musculus cell adhesion molecule 2 (Cadm2), transcript variant X4,...
PREDICTED: Mus musculus cell adhesion molecule 2 (Cadm2), transcript variant X4, mRNA
gi|1907117846|ref|XM_011246129.4|

Nucleotide
autophagy-related 4B (yeast), isoform CRA_d [Rattus norvegicus]
autophagy-related 4B (yeast), isoform CRA_d [Rattus norvegicus]
gi|149037476|gb|EDL91907.1||gnl|WGS |rCP24402

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001733783	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001733783

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 28, 2020)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001733783.1

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

Description

This missense variant (also known as p.Asn309Asp in the mature protein) replaces asparagine with aspartic acid at codon 330 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 not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 1/251044 chromosomes 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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