NM_000527.5(LDLR):c.907C>T (p.Arg303Trp) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 1, 2026
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000657894.19

Allele description [Variation Report for NM_000527.5(LDLR):c.907C>T (p.Arg303Trp)]

NM_000527.5(LDLR):c.907C>T (p.Arg303Trp)

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.907C>T (p.Arg303Trp)

Other names:

NM_000527.5(LDLR):c.907C>T

HGVS:

NC_000019.10:g.11107481C>T
NG_009060.1:g.23101C>T
NM_000527.5:c.907C>TMANE SELECT
NM_001195798.2:c.907C>T
NM_001195799.2:c.784C>T
NM_001195800.2:c.403C>T
NM_001195803.2:c.526C>T
NP_000518.1:p.Arg303Trp
NP_000518.1:p.Arg303Trp
NP_001182727.1:p.Arg303Trp
NP_001182728.1:p.Arg262Trp
NP_001182729.1:p.Arg135Trp
NP_001182732.1:p.Arg176Trp
LRG_274t1:c.907C>T
LRG_274:g.23101C>T
LRG_274p1:p.Arg303Trp
NC_000019.9:g.11218157C>T
NM_000527.4:c.907C>T
c.907C>T
p.Arg303Trp

Protein change:

R135W

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000512; dbSNP: rs151207122

Molecular consequence:

NM_000527.5:c.907C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.907C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.784C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.403C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.526C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779658	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 1, 2026)	germline	clinical testing	Citation Link,
SCV001715243	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV007111011	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Sep 19, 2025)	unknown	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

SCV000779658

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 1, 2026)

germline

clinical testing

Citation Link,

SCV001715243

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 11, 2022)

germline

clinical testing

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

SCV007111011

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Sep 19, 2025)

unknown

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	4	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000779658.6

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.(R282W); This variant is associated with the following publications: (PMID: 25637381, 25487149, 31106297, 32977124, 32719484, 33955087, 24507775, 35741760, 34040191, 36507290, 28965616, 9544746, 37409534)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001715243.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (1)

Description

PP3

#	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		4	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV007111011.1

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

Description

The LDLR c.907C>T (p.Arg303Trp) variant has been reported in the published literature in individuals with familial hypercholesterolemia (FH) (PMID: 9544746 (1998), 25637381 (2015), 28965616 (2017), 31106297 (2018), 31345425 (2019), 33079599 (2020), 33955087 (2021), 34040191 (2021), 35741760 (2022), and 36184534 (2022)). It has also been described in individuals with homozygous familial hypercholesterolemia (hoFH) (PMIDs: 32977124 (2020) and 36507290 (2022)), as well as in an individual with early age myocardial infarction (PMID: 25487149 (2015)).The frequency of this variant in the general population (Genome Aggregation Database, http://gnomad.broadinstitute.org) is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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