NM_000527.5(LDLR):c.2483A>G (p.Tyr828Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 6, 2022
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:: RCV000162025.4

Allele description [Variation Report for NM_000527.5(LDLR):c.2483A>G (p.Tyr828Cys)]

NM_000527.5(LDLR):c.2483A>G (p.Tyr828Cys)

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.2483A>G (p.Tyr828Cys)

Other names:

Y807C; FH Bari; FH Syria; FHJ.D-Bari

HGVS:

NC_000019.10:g.11129606A>G
NG_009060.1:g.45226A>G
NM_000527.5:c.2483A>GMANE SELECT
NM_001195798.2:c.2483A>G
NM_001195799.2:c.2360A>G
NM_001195800.2:c.1979A>G
NM_001195803.2:c.1949A>G
NP_000518.1:p.Tyr828Cys
NP_000518.1:p.Tyr828Cys
NP_001182727.1:p.Tyr828Cys
NP_001182728.1:p.Tyr787Cys
NP_001182729.1:p.Tyr660Cys
NP_001182732.1:p.Tyr650Cys
LRG_274t1:c.2483A>G
LRG_274:g.45226A>G
LRG_274p1:p.Tyr828Cys
NC_000019.9:g.11240282A>G
NM_000527.4:c.2483A>G
P01130:p.Tyr828Cys
c.2483A>G

Protein change:

Y650C; TYR807CYS

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000307; UniProtKB: P01130#VAR_005419; OMIM: 606945.0019

Molecular consequence:

NM_000527.5:c.2483A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2483A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.2360A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1979A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1949A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

unknown functional consequence - Comment(s)

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
SCV000189628	Dept. of Genetics and Pharmacogenomics, Merck Research Labs See additional submitters Runz lab, Institute of Human Genetics, Heidelberg	no classification provided (in vitro)	not provided	not applicable	in vitro	PubMed (1) [See all records that cite this PMID]
SCV002520116	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 6, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000189628

Dept. of Genetics and Pharmacogenomics, Merck Research Labs

See additional submitters

no classification provided

(in vitro)

not provided

not applicable

in vitro

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

SCV002520116

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 6, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Systematic cell-based phenotyping of missense alleles empowers rare variant association studies: a case for LDLR and myocardial infarction.

Thormaehlen AS, Schuberth C, Won HH, Blattmann P, Joggerst-Thomalla B, Theiss S, Asselta R, Duga S, Merlini PA, Ardissino D, Lander ES, Gabriel S, Rader DJ, Peloso GM, Pepperkok R, Kathiresan S, Runz H.

PLoS Genet. 2015 Feb;11(2):e1004855. doi: 10.1371/journal.pgen.1004855. Erratum in: PLoS Genet. 2015 Mar;11(3):e1005060.

PubMed [citation]

PMID:: 25647241
PMCID:: PMC4409815

Details of each submission

From Dept. of Genetics and Pharmacogenomics, Merck Research Labs, SCV000189628.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

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

From GeneDx, SCV002520116.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect through defective uptake, internalization, and degradation (Davis et al., 1986; Ranheim et al., 2006; Thormaehlen et al., 2015); Also denoted as Y807C and FH J.D-Bari due to the use of alternate nomenclature; This variant is associated with the following publications: (PMID: 23375686, 28126585, 23733886, 189940, 8882879, 19446849, 200368, 31387896, 20145306, 25461735, 3955657, 23105264, 32041611, 33740630, 32719484, 33508743, Thajer2022, 25647241, 16740646)

#	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

Last Updated: Mar 16, 2024

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