NM_000130.4(F5):c.1601G>A (p.Arg534Gln) AND Factor V deficiency

Germline classification:: Pathogenic; risk factor (3 submissions)
Last evaluated:: Mar 4, 2020
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:: RCV000205002.29

Allele description [Variation Report for NM_000130.4(F5):c.1601G>A (p.Arg534Gln)]

NM_000130.4(F5):c.1601G>A (p.Arg534Gln)

Gene:

F5:coagulation factor V [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q24.2

Genomic location:

Preferred name:

NM_000130.4(F5):c.1601G>A (p.Arg534Gln)

Other names:

F5, ARG506GLN; R506Q; F5:c.1601G>A (p.Arg534Gln); factor V Leiden

HGVS:

NC_000001.11:g.169549811C>T
NG_011806.1:g.41721G>A
NM_000130.5:c.1601G>AMANE SELECT
NP_000121.2:p.Arg534Gln
NP_000121.2:p.Arg534Gln
LRG_553t1:c.1601G>A
LRG_553:g.41721G>A
NC_000001.10:g.169519049=
NC_000001.10:g.169519049T=
NM_000130.4:c.1601G>A
NM_00130.4:c.1601G>A
P12259:p.Arg534Gln
p.Arg506Gln
p.Gln534=

Protein change:

R534Q; ARG506GLN

Links:

Genetic Testing Registry (GTR): GTR000509357; Genetic Testing Registry (GTR): GTR000613302; UniProtKB: P12259#VAR_001213; OMIM: 612309.0001; dbSNP: rs6025

NCBI 1000 Genomes Browser:

rs6025

Molecular consequence:

NM_000130.5:c.1601G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Factor V deficiency
Synonyms:: Reduced coagulation factor V activity
Identifiers:: MONDO: MONDO:0020586; MedGen: C4317320; Orphanet: 326; Human Phenotype Ontology: HP:0003225

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000271297	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	risk factor (Mar 4, 2020)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 23900608, 21116184, 12070000, 19652888, 23382263, 26251307, 11110695, 20051284, 21774968, 24033266
SCV000839955	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 13, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001525756	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 24, 2018)	maternal	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8164741, 26990548, 25977387, 26251307, 23677252, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271297

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

risk factor
(Mar 4, 2020)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV000839955

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 13, 2017)

germline

clinical testing

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

SCV001525756

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 24, 2018)

maternal

clinical testing

PubMed (6)
[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	9	9	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls.

Simone B, De Stefano V, Leoncini E, Zacho J, Martinelli I, Emmerich J, Rossi E, Folsom AR, Almawi WY, Scarabin PY, den Heijer M, Cushman M, Penco S, Vaya A, Angchaisuksiri P, Okumus G, Gemmati D, Cima S, Akar N, Oguzulgen KI, Ducros V, Lichy C, et al.

Eur J Epidemiol. 2013 Aug;28(8):621-47. doi: 10.1007/s10654-013-9825-8. Epub 2013 Jul 31.

PubMed [citation]

PMID:: 23900608
PMCID:: PMC3935237

Factor V Leiden thrombophilia.

Kujovich JL.

Genet Med. 2011 Jan;13(1):1-16. doi: 10.1097/GIM.0b013e3181faa0f2. Review.

PubMed [citation]

PMID:: 21116184

See all PubMed Citations (15)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271297.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	9	not provided	not provided	clinical testing	PubMed (10)

Description

F5 c.1601G>A (p.Arg534Gln; commonly known as Factor V Leiden, historically reported as p.Arg506Gln) has been associated with increased risk for venous thromboembolism (VTE). This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of European ancestry (2.96%, Genome Aggregation Database (gnomAD); rs6025) and is present in ClinVar (ID: 642). Several meta-analyses and case-control studies have reported odds ratios between 2.2-4.93 for developing VTE in heterozygous carriers (OR=2.2 [95% CI 2.0-2.5] Sode 2013, OR=4.22 [95% CI 3.35-5.32] Simone 2013, OR=4.93 [95% CI 4.41-5.52] Gohil 2009, OR= 2.4 [95% CI 1.3â€“3.8] Juul 2004) and odds ratios between 7-11.5 for developing VTE in homozygous carriers (OR=7.0 [95% CI 4.8-10] Sode 2013, OR=11.45 [95% CI 6.79-19.29] Simone 2013). In vivo and in vitro functional studies provide evidence that the Factor V Leiden variant impacts protein function (Dirven 2010, Cui 2000, Banno 2015, Koncz 2012). In summary, the p.Arg534Gln variant meets criteria for classification as an established risk allele for VTE.

#	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		9	not provided	9	not provided

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000839955.1

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

Description

This c.1601G>A (p.Arg534Gln) variant is known as the Factor V Leiden variant (legacy name p.Arg506Gln). Factor V Leiden variant is associated with thrombophilia due to activated protein C resistance [MIM:188055]. Studies suggest that the relative risk for venous thrombosis associated with the factor V Leiden variant in the absence of other acquired or environmental predispositions is approximately 4- to 7-fold for heterozygotes and 80-fold for homozygotes (PMID 16024978). This variant is classified as pathogenic. Homozygosity for this variant is also considered medically actionable.

#	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 Baylor Genetics, SCV001525756.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been known as the Factor V Leiden variant [PMID 8164741, 26990548, 25977387, 26251307, 23677252, Factor V Leiden]

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

Last Updated: Nov 30, 2024

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