NM_000527.5(LDLR):c.1130G>T (p.Cys377Phe) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 24, 2021
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:: RCV000505209.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1130G>T (p.Cys377Phe)]

NM_000527.5(LDLR):c.1130G>T (p.Cys377Phe)

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.1130G>T (p.Cys377Phe)

HGVS:

NC_000019.10:g.11111583G>T
NG_009060.1:g.27203G>T
NM_000527.5:c.1130G>TMANE SELECT
NM_001195798.2:c.1130G>T
NM_001195799.2:c.1007G>T
NM_001195800.2:c.626G>T
NM_001195803.2:c.749G>T
NP_000518.1:p.Cys377Phe
NP_000518.1:p.Cys377Phe
NP_001182727.1:p.Cys377Phe
NP_001182728.1:p.Cys336Phe
NP_001182729.1:p.Cys209Phe
NP_001182732.1:p.Cys250Phe
LRG_274t1:c.1130G>T
LRG_274:g.27203G>T
LRG_274p1:p.Cys377Phe
NC_000019.9:g.11222259G>T
NM_000527.4:c.1130G>T
p.(Cys377Phe)

Protein change:

C209F

Links:

dbSNP: rs879254801

NCBI 1000 Genomes Browser:

rs879254801

Molecular consequence:

NM_000527.5:c.1130G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1130G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1007G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.626G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.749G>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000599362	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 1, 2016)	germline, not applicable	curation, literature only	PubMed (2) [See all records that cite these PMIDs] 25741868, 21865347
SCV001653623	Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21865347, 32977124, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000599362

Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 1, 2016)

germline, not applicable

curation, literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001653623

Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 24, 2021)

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	not provided	not provided	not provided	not provided	not provided	curation
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	literature only
Caucasian	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations.

Romano M, Di Taranto MD, Mirabelli P, D'Agostino MN, Iannuzzi A, Marotta G, Gentile M, Raia M, Di Noto R, Del Vecchio L, Rubba P, Fortunato G.

J Lipid Res. 2011 Nov;52(11):2095-100. doi: 10.1194/jlr.D017772. Epub 2011 Aug 24.

PubMed [citation]

PMID:: 21865347
PMCID:: PMC3196240

Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features.

Bertolini S, Calandra S, Arca M, Averna M, Catapano AL, Tarugi P; Italian Study Group of Homozygous Familial Hypercholesterolemia..

Atherosclerosis. 2020 Nov;312:72-78. doi: 10.1016/j.atherosclerosis.2020.08.027. Epub 2020 Sep 9.

PubMed [citation]

PMID:: 32977124

See all PubMed Citations (3)

Details of each submission

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599362.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)
2	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

"Assay Description:Htz patients' Epstein-Barr virus transformed lymphocytes, FACS assays"

PubMed [ID: 21865347]

#	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
2	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II, SCV001653623.1

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

#	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		2	not provided	not provided	not provided

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine