NM_000527.5(LDLR):c.388T>C (p.Ser130Pro) AND Hypercholesterolemia, familial, 1

Germline classification:: Conflicting interpretations of pathogenicity (2 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:: RCV000237659.4

Allele description [Variation Report for NM_000527.5(LDLR):c.388T>C (p.Ser130Pro)]

NM_000527.5(LDLR):c.388T>C (p.Ser130Pro)

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.388T>C (p.Ser130Pro)

HGVS:

NC_000019.10:g.11105294T>C
NG_009060.1:g.20914T>C
NM_000527.5:c.388T>CMANE SELECT
NM_001195798.2:c.388T>C
NM_001195799.2:c.265T>C
NM_001195800.2:c.314-2098T>C
NM_001195803.2:c.314-1271T>C
NP_000518.1:p.Ser130Pro
NP_000518.1:p.Ser130Pro
NP_001182727.1:p.Ser130Pro
NP_001182728.1:p.Ser89Pro
LRG_274t1:c.388T>C
LRG_274:g.20914T>C
LRG_274p1:p.Ser130Pro
NC_000019.9:g.11215970T>C
NM_000527.4:c.388T>C
c.388T>C

Protein change:

S130P

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000985; dbSNP: rs879254508

NCBI 1000 Genomes Browser:

rs879254508

Molecular consequence:

NM_001195800.2:c.314-2098T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1271T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.388T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.388T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.265T>C - 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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heme biosynthesis protein HemY [Alcaligenes ammonioxydans]
heme biosynthesis protein HemY [Alcaligenes ammonioxydans]
gi|2072648347|gnl|PRJNA543690|FE795 0|gb|QXX79356.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000294679	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely benign (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000540730	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)	Uncertain significance (Nov 5, 2016)	inherited	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25741868, 22698793, 11754108

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000294679

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely benign
(Mar 25, 2016)

germline

literature only

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

Citation Link,

SCV000540730

Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 5, 2016)

inherited

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	yes	1	not provided	not provided	1	not provided	literature only
Caucasian	inherited	yes	6	4	not provided	3964	yes	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

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, SCV000294679.2

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

#	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

From Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, SCV000540730.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	6	not provided	yes	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	3964	Whole blood	not provided		6	not provided	4	not provided

Last Updated: Feb 4, 2024

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