NM_000130.4(F5):c.1321C>T (p.Arg441Cys) AND Factor V deficiency

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Feb 1, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000778946.2

Allele description [Variation Report for NM_000130.4(F5):c.1321C>T (p.Arg441Cys)]

NM_000130.4(F5):c.1321C>T (p.Arg441Cys)

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.1321C>T (p.Arg441Cys)
HGVS:
  • NC_000001.11:g.169550715G>A
  • NG_011806.1:g.40817C>T
  • NM_000130.4:c.1321C>T
  • NP_000121.2:p.Arg441Cys
  • LRG_553t1:c.1321C>T
  • LRG_553:g.40817C>T
  • LRG_553p1:p.Arg441Cys
  • NC_000001.10:g.169519953G>A
Protein change:
R441C
Links:
dbSNP: rs747006175
NCBI 1000 Genomes Browser:
rs747006175
Molecular consequence:
  • NM_000130.4:c.1321C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Factor V deficiency
Synonyms:
LABILE FACTOR DEFICIENCY; OWREN PARAHEMOPHILIA; PARAHEMOPHILIA
Identifiers:
MedGen: C0015499; Orphanet: 326; OMIM: 227400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000899477NIHR Bioresource Rare Diseases, University of Cambridge - ThromboGenomicscriteria provided, single submitter
Likely pathogenic
(Feb 1, 2019)
unknownresearch

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

SCV000915368Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Dec 5, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Europeanunknownyes1not providednot provided1not providedresearch

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

Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.

Downes K, Megy K, Duarte D, Vries M, Gebhart J, Hofer S, Shamardina O, Deevi SVV, Stephens J, Mapeta R, Tuna S, Al Hasso N, Besser MW, Cooper N, Daugherty L, Gleadall N, Greene D, Haimel M, Martin H, Papadia S, Revel-Vilk S, Sivapalaratnam S, et al.

Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.

PubMed [citation]
PMID:
31064749
PMCID:
PMC6993014
See all PubMed Citations (4)

Details of each submission

From NIHR Bioresource Rare Diseases, University of Cambridge - ThromboGenomics, SCV000899477.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1European1not providednot providedresearch PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes1not providednot provided1not providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000915368.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The F5 c.1321C>T (p.Arg441Cys) missense variant has been reported in two studies in which it is found in two individuals affected with factor V deficiency, including one each in a compound heterozygous and heterozygous state (Jin et al. 2009; Delev at al. 2009). The proband reported in Jin et al. (2009) inherited the p.Arg441Cys variant from his unaffected mother and the second missense variant from his unaffected father. The proband's unaffected child was also heterozygous for the p.Arg441Cys variant. Control data are unavailable for this variant, which is reported at a frequency of 0.000239 in the European (Finnish) population of the Genome Aggregation Database. Based on the limited evidence, the p.Arg441Cys variant is classified as a variant of unknown significance but suspicious for pathogenicity for factor V deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 12, 2021

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