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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003445264	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 23, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1346077, 18624698, 19699296, 32875744, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003445264

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 23, 2022)

germline

clinical testing

PubMed (5)
[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	not provided	not provided	not provided	not provided	not provided	clinical 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

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

#	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

Last Updated: Oct 26, 2024

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