NM_174936.4(PCSK9):c.45GCT[9] (p.Leu22_Leu23dup) AND Hypercholesterolemia, familial, 1

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jan 2, 2018
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:: RCV000256321.15

Allele description [Variation Report for NM_174936.4(PCSK9):c.45GCT[9] (p.Leu22_Leu23dup)]

NM_174936.4(PCSK9):c.45GCT[9] (p.Leu22_Leu23dup)

Gene:

PCSK9:proprotein convertase subtilisin/kexin type 9 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

1p32.3

Genomic location:

Preferred name:

NM_174936.4(PCSK9):c.45GCT[9] (p.Leu22_Leu23dup)

HGVS:

NC_000001.10:g.55505570_55505575dup
NC_000001.11:g.55039882GCT[9]
NG_009061.1:g.5336GCT[9]
NG_009061.1:g.5351_5356dup
NM_174936.4:c.45GCT[9]MANE SELECT
NP_777596.2:p.Leu22_Leu23dup
LRG_275:g.5336GCT[9]
NC_000001.10:g.55505552_55505553insCTGCTG
NC_000001.10:g.55505555GCT[9]
NC_000001.10:g.55505570_55505575dup
NC_000001.11:g.55039902_55039903insGCTGCT
NG_009061.1:g.5351_5356dup
NM_174936.3:c.60_65dupGCTGCT

Links:

dbSNP: rs35574083

NCBI 1000 Genomes Browser:

rs35574083

Molecular consequence:

NM_174936.4:c.45GCT[9] - inframe_insertion - [Sequence Ontology: SO:0001821]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000323027	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000606671	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Benign	germline	research
SCV000690982	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 7, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000782987	Robarts Research Institute, Western University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jan 2, 2018)	germline	clinical testing	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	unknown	not provided	not provided	not provided	not provided	not provided	research, clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research

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

Details of each submission

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000323027.1

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

Description

%MAF (ExAC):0.2212

Description

0/100 French Canadian and 0/100 French normolipidemic and trigliceridemic controls; 0/100 Tunisian normolipidemic individuals

#	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
2	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606671.1

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

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000690982.2

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

From Robarts Research Institute, Western University, SCV000782987.1

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

#	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: Jun 2, 2024

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