NM_174936.4(PCSK9):c.720C>T (p.Gly240=) 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:: RCV000256304.11

Allele description [Variation Report for NM_174936.4(PCSK9):c.720C>T (p.Gly240=)]

NM_174936.4(PCSK9):c.720C>T (p.Gly240=)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p32.3

Genomic location:

Preferred name:

NM_174936.4(PCSK9):c.720C>T (p.Gly240=)

HGVS:

NC_000001.11:g.55052712C>T
NG_009061.1:g.18166C>T
NM_001407240.1:c.843C>T
NM_001407241.1:c.720C>T
NM_001407242.1:c.723C>T
NM_001407243.1:c.663C>T
NM_001407244.1:c.720C>T
NM_001407245.1:c.528C>T
NM_001407246.1:c.345C>T
NM_001407247.1:c.720C>T
NM_174936.4:c.720C>TMANE SELECT
NP_001394169.1:p.Gly281=
NP_001394170.1:p.Gly240=
NP_001394171.1:p.Gly241=
NP_001394172.1:p.Gly221=
NP_001394173.1:p.Gly240=
NP_001394174.1:p.Gly176=
NP_001394175.1:p.Gly115=
NP_001394176.1:p.Gly240=
NP_777596.2:p.Gly240=
NP_777596.2:p.Gly240=
LRG_275t1:c.720C>T
LRG_275:g.18166C>T
LRG_275p1:p.Gly240=
NC_000001.10:g.55518385C>T
NM_174936.3:c.720C>T
NR_110451.3:n.1053C>T
NR_176318.1:n.694C>T
NR_176319.1:n.1010C>T
NR_176320.1:n.1133C>T
NR_176321.1:n.1010C>T
NR_176322.1:n.1010C>T
NR_176323.1:n.1010C>T
NR_176324.1:n.1272C>T

Links:

dbSNP: rs41297883

NCBI 1000 Genomes Browser:

rs41297883

Molecular consequence:

NR_110451.3:n.1053C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176318.1:n.694C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176319.1:n.1010C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176320.1:n.1133C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176321.1:n.1010C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176322.1:n.1010C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176323.1:n.1010C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176324.1:n.1272C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001407240.1:c.843C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407241.1:c.720C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407242.1:c.723C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407243.1:c.663C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407244.1:c.720C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407245.1:c.528C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407246.1:c.345C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001407247.1:c.720C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_174936.4:c.720C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000323053	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]
SCV000690988	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 2, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000748118	Iberoamerican FH Network	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000782993	Robarts Research Institute, Western University	criteria provided, single submitter (ACMG Guidelines, 2015)	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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research, 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

Details of each submission

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000323053.1

#	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):0.54

#	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 Color Diagnostics, LLC DBA Color Health, SCV000690988.2

#	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 Iberoamerican FH Network, SCV000748118.1

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

Description

%MAF(ExAC):0.54

#	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, SCV000782993.1

#	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: Apr 15, 2024

ClinVar

Relating variation to medicine