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NM_000133.4(F9):c.676C>T (p.Arg226Trp) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 23, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002512970.10

Allele description [Variation Report for NM_000133.4(F9):c.676C>T (p.Arg226Trp)]

NM_000133.4(F9):c.676C>T (p.Arg226Trp)

Gene:
F9:coagulation factor IX [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq27.1
Genomic location:
Preferred name:
NM_000133.4(F9):c.676C>T (p.Arg226Trp)
Other names:
F9, ARG180TRP; R180W
HGVS:
  • NC_000023.11:g.139551217C>T
  • NG_007994.1:g.25482C>T
  • NM_000133.4:c.676C>TMANE SELECT
  • NM_001313913.2:c.562C>T
  • NP_000124.1:p.Arg226Trp
  • NP_001300842.1:p.Arg188Trp
  • LRG_556t1:c.676C>T
  • LRG_556:g.25482C>T
  • NC_000023.10:g.138633376C>T
  • NM_000133.3:c.676C>T
  • P00740:p.Arg226Trp
Protein change:
R188W; ARG180TRP
Links:
UniProtKB: P00740#VAR_006570; OMIM: 300746.0030; dbSNP: rs137852240
NCBI 1000 Genomes Browser:
rs137852240
Molecular consequence:
  • NM_000133.4:c.676C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001313913.2:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary factor IX deficiency disease (HEMB)
Synonyms:
F9 DEFICIENCY; PLASMA THROMBOPLASTIN COMPONENT DEFICIENCY; Hemophilia B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010604; MeSH: D002836; MedGen: C0008533; Orphanet: 98879; OMIM: 306900
Name:
Thrombophilia, X-linked, due to factor 9 defect
Synonyms:
Thrombophilia, X-linked, due to factor IX defect
Identifiers:
MONDO: MONDO:0010432; MedGen: C2749016; OMIM: 300807

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003445264Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Apr 23, 2022)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Parental origin of factor IX gene mutations, and their distribution in the gene.

Ludwig M, Grimm T, Brackmann HH, Olek K.

Am J Hum Genet. 1992 Jan;50(1):164-73.

PubMed [citation]
PMID:
1346077
PMCID:
PMC1682539

Identification of mutations in the F9 gene including exon deletion by multiplex ligation-dependent probe amplification in 33 unrelated Korean patients with haemophilia B.

Kwon MJ, Yoo KY, Kim HJ, Kim SH.

Haemophilia. 2008 Sep;14(5):1069-75. doi: 10.1111/j.1365-2516.2008.01796.x. Epub 2008 Jul 8.

PubMed [citation]
PMID:
18624698
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445264.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 226 of the F9 protein (p.Arg226Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hemophilia B (PMID: 1346077, 18624698, 19699296, 32875744). This variant is also known as C20518T (180 R>W).. ClinVar contains an entry for this variant (Variation ID: 10590). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Arg226 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 32875744), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 26, 2024