NM_000527.5(LDLR):c.1865A>G (p.Asp622Gly) AND Hypercholesterolemia, familial, 1

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Nov 5, 2016
Review status:: criteria provided, conflicting classifications

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:: RCV000237397.4

Allele description [Variation Report for NM_000527.5(LDLR):c.1865A>G (p.Asp622Gly)]

NM_000527.5(LDLR):c.1865A>G (p.Asp622Gly)

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.1865A>G (p.Asp622Gly)

HGVS:

NC_000019.10:g.11120111A>G
NG_009060.1:g.35731A>G
NM_000527.5:c.1865A>GMANE SELECT
NM_001195798.2:c.1865A>G
NM_001195799.2:c.1742A>G
NM_001195800.2:c.1361A>G
NM_001195803.2:c.1484A>G
NP_000518.1:p.Asp622Gly
NP_000518.1:p.Asp622Gly
NP_001182727.1:p.Asp622Gly
NP_001182728.1:p.Asp581Gly
NP_001182729.1:p.Asp454Gly
NP_001182732.1:p.Asp495Gly
LRG_274t1:c.1865A>G
LRG_274:g.35731A>G
LRG_274p1:p.Asp622Gly
NC_000019.9:g.11230787A>G
NM_000527.4:c.1865A>G
c.1865A>G

Protein change:

D454G

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000256; dbSNP: rs879255060

NCBI 1000 Genomes Browser:

rs879255060

Molecular consequence:

NM_000527.5:c.1865A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1865A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1742A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1361A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1484A>G - 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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gi|126259186|gnl|dbEST|45038362|gb| 810.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295727	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 19318025, 22698793 Citation Link,
SCV000540847	Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation See additional submitters Centre of Molecular Biology and Gene Therapy, University Hospital Brno	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 5, 2016)	inherited	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 22698793
SCV000607650	Fundacion Hipercolesterolemia Familiar - SAFEHEART	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295727

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely pathogenic
(Mar 25, 2016)

germline

literature only

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

Citation Link,

SCV000540847

Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 5, 2016)

inherited

clinical testing

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

SCV000607650

Fundacion Hipercolesterolemia Familiar - SAFEHEART

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 1, 2016)

germline

research

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	yes	2	not provided	not provided	2	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research
Caucasian	inherited	yes	2	1	not provided	3964	yes	clinical testing

Citations

PubMed

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19318025

The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations.

Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2012 Aug;223(2):401-8. doi: 10.1016/j.atherosclerosis.2012.05.014. Epub 2012 May 23.

PubMed [citation]

PMID:: 22698793

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295727.2

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

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

From Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, SCV000540847.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	3964	Whole blood	not provided		2	not provided	1	not provided

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607650.1

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

#	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

Last Updated: May 1, 2024

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