NM_000527.5(LDLR):c.1241T>G (p.Leu414Arg) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 20, 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:: RCV003477854.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1241T>G (p.Leu414Arg)]

NM_000527.5(LDLR):c.1241T>G (p.Leu414Arg)

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.1241T>G (p.Leu414Arg)

Other names:

NP_000518.1:p.L414R; NM_000527.5(LDLR):c.1241T>G

HGVS:

NC_000019.10:g.11113332T>G
NG_009060.1:g.28952T>G
NM_000527.5:c.1241T>GMANE SELECT
NM_001195798.2:c.1241T>G
NM_001195799.2:c.1118T>G
NM_001195800.2:c.737T>G
NM_001195803.2:c.860T>G
NP_000518.1:p.Leu414Arg
NP_000518.1:p.Leu414Arg
NP_001182727.1:p.Leu414Arg
NP_001182728.1:p.Leu373Arg
NP_001182729.1:p.Leu246Arg
NP_001182732.1:p.Leu287Arg
LRG_274t1:c.1241T>G
LRG_274:g.28952T>G
LRG_274p1:p.Leu414Arg
NC_000019.9:g.11224008T>G
NM_000527.4:c.1241T>G
P01130:p.Leu414Arg
c.1241T>G

Protein change:

L246R

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000372; UniProtKB: P01130#VAR_005379; dbSNP: rs748554592

NCBI 1000 Genomes Browser:

rs748554592

Molecular consequence:

NM_000527.5:c.1241T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1241T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1118T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.737T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.860T>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004219940	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (Sep 20, 2023)	unknown	clinical testing	PubMed (14) [See all records that cite these PMIDs] 36325061, 35130036, 29353225, 27765764, 18022922, 9763532, 26875521, 11005141, 30592178, 34037665, 36229885, 33994402, 33892292, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004219940

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely pathogenic
(Sep 20, 2023)

unknown

clinical testing

PubMed (14)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Low-density lipoprotein receptor genotypes modify the sera metabolome of patients with homozygous familial hypercholesterolemia.

Du Z, Li F, Li L, Wang Y, Li J, Yang Y, Jiang L, Wang L, Qin Y.

iScience. 2022 Nov 18;25(11):105334. doi: 10.1016/j.isci.2022.105334.

PubMed [citation]

PMID:: 36325061
PMCID:: PMC9618791

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort.

Tomar S, Klinzing DC, Chen CK, Gan LH, Moscarello T, Reuter C, Ashley EA, Foo R.

Circ Genom Precis Med. 2022 Apr;15(2):e003536. doi: 10.1161/CIRCGEN.121.003536. Epub 2022 Feb 7.

PubMed [citation]

PMID:: 35130036

See all PubMed Citations (14)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219940.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

Description

The LDLR c.1241T>G (p.Leu414Arg) variant has been reported in the published literature in multiple individuals affected with familial hypercholesterolemia (PMIDs: 9763532 (1998), 11005141 (2000), 18022922 (2007), 26875521 (2016), 30592178 (2019), 33994402 (2021), 35130036 (2022), 36229885 (2022), 36325061 (2022)). The frequency of this variant in the general population, 0.000008 (2/251172 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with 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, this variant is classified as likely pathogenic.

#	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: Nov 3, 2024

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