NM_000527.5(LDLR):c.395G>A (p.Arg132Gln) AND Hypercholesterolemia, familial, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 3, 2023
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:: RCV004008794.2

Allele description [Variation Report for NM_000527.5(LDLR):c.395G>A (p.Arg132Gln)]

NM_000527.5(LDLR):c.395G>A (p.Arg132Gln)

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.395G>A (p.Arg132Gln)

HGVS:

NC_000019.10:g.11105301G>A
NG_009060.1:g.20921G>A
NM_000527.5:c.395G>AMANE SELECT
NM_001195798.2:c.395G>A
NM_001195799.2:c.272G>A
NM_001195800.2:c.314-2091G>A
NM_001195803.2:c.314-1264G>A
NP_000518.1:p.Arg132Gln
NP_001182727.1:p.Arg132Gln
NP_001182728.1:p.Arg91Gln
LRG_274t1:c.395G>A
LRG_274:g.20921G>A
NC_000019.9:g.11215977G>A
NM_000527.4:c.395G>A

Protein change:

R132Q

Links:

dbSNP: rs751519676

NCBI 1000 Genomes Browser:

rs751519676

Molecular consequence:

NM_001195800.2:c.314-2091G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1264G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.395G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.395G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.272G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Mus musculus small nuclear ribonucleoprotein N (Snrpn), transcript variant 4, mR...
Mus musculus small nuclear ribonucleoprotein N (Snrpn), transcript variant 4, mRNA
gi|1167503309|ref|NM_001349690.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004820160	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Apr 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29399563, 32331935, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004820160

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Apr 3, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Detection of Familial Hypercholesterolemia Using Next Generation Sequencing in Two Population-Based Cohorts.

Kim HN, Kweon SS, Shin MH.

Chonnam Med J. 2018 Jan;54(1):31-35. doi: 10.4068/cmj.2018.54.1.31. Epub 2018 Jan 25.

PubMed [citation]

PMID:: 29399563
PMCID:: PMC5794476

A catalog of the pathogenic mutations of LDL receptor gene in Japanese familial hypercholesterolemia.

Tada H, Hori M, Nomura A, Hosomichi K, Nohara A, Kawashiri MA, Harada-Shiba M.

J Clin Lipidol. 2020 May - Jun;14(3):346-351.e9. doi: 10.1016/j.jacl.2020.03.002. Epub 2020 Mar 24.

PubMed [citation]

PMID:: 32331935

See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004820160.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant (also known as p.Arg111Gln in the mature protein) replaces arginine with glutamine at codon 132 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 been reported in three individuals affected with familial hypercholesterolemia (PMID: 29399563, 32331935). This variant has been identified in 5/251144 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	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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