VCV000016404.22 - ClinVar

NM_021871.4(FGA):c.104G>A (p.Arg35His)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_021871.4(FGA):c.104G>A (p.Arg35His)

Variation ID: 16404 Accession: VCV000016404.22

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4q31.3 4: 154589513 (GRCh38) [ NCBI UCSC ] 4: 155510665 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 9, 2018	Oct 8, 2024	Apr 9, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_021871.4:c.104G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_068657.1:p.Arg35His	missense
NM_000508.5:c.104G>A	NP_000499.1:p.Arg35His	missense
NC_000004.12:g.154589513C>T
NC_000004.11:g.155510665C>T
NG_008832.1:g.6233G>A
LRG_557:g.6233G>A
LRG_557t1:c.104G>A	LRG_557p1:p.Arg35His
LRG_557t2:c.104G>A
	P02671:p.Arg35His

... more HGVS ... less HGVS

Protein change

R35H

Other names

R16H
FIBRINOGEN AMIENS 1
FIBRINOGEN AMIENS 2
FIBRINOGEN BERGAMO 3
FIBRINOGEN BERN 2
FIBRINOGEN BICETRE 1
FIBRINOGEN BIRMINGHAM 1
FIBRINOGEN CHAPEL HILL 2
FIBRINOGEN CLERMONT-FERRAND 1
FIBRINOGEN GIESSEN 1
FIBRINOGEN LEITCHFIELD
FIBRINOGEN LONG BEACH 1
FIBRINOGEN LOUISVILLE 1
FIBRINOGEN MANCHESTER 1
FIBRINOGEN PARIS 6
FIBRINOGEN PETOSKEY 1
FIBRINOGEN SEATTLE 2
FIBRINOGEN SHEFFIELD 2
FIBRINOGEN SYDNEY 1
FIBRINOGEN SYDNEY 2
FIBRINOGEN WHITE MARSH 1
Fibrinogen Petoskey

Canonical SPDI

NC_000004.12:154589512:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Links

ClinGen: CA130224 UniProtKB: P02671#VAR_002393 OMIM: 134820.0004 dbSNP: rs121909607 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FGA		-	-	GRCh38 GRCh37	230	262

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Dysfibrinogenemia	Pathogenic (1)	no assertion criteria provided	Jul 1, 1989	RCV000030941.8
Hypofibrinogenemia	Pathogenic (1)	criteria provided, single submitter	Feb 1, 2019	RCV000851581.1
Abnormal bleeding	Pathogenic (1)	criteria provided, single submitter	Feb 1, 2019	RCV000851971.1
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Apr 9, 2024	RCV001509236.12
Familial dysfibrinogenemia	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Aug 29, 2022	RCV002228034.3
Congenital afibrinogenemia Familial dysfibrinogenemia Familial visceral amyloidosis, Ostertag type	Pathogenic (1)	criteria provided, single submitter	Apr 20, 2022	RCV002476987.1
FGA-related disorder	Pathogenic (1)	no assertion criteria provided	May 28, 2024	RCV004532379.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Feb 01, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Hypofibrinogenemia Affected status: yes Allele origin: unknown	NIHR Bioresource Rare Diseases, University of Cambridge Study: ThromboGenomics Accession: SCV000899295.1 First in ClinVar: Sep 29, 2019 Last updated: Sep 29, 2019	Publications: PubMed (1) PubMed: 31064749 Observation 1: Observation 2: Ethnicity/Population group: European Observation 3: Sex: female Ethnicity/Population group: European Observation 4: Sex: female Ethnicity/Population group: South-Asian,European Observation 5: Sex: female Ethnicity/Population group: European Observation 6: Sex: male Ethnicity/Population group: European Observation 7: Sex: male Ethnicity/Population group: South-Asian Observation 8: Sex: male Ethnicity/Population group: European Observation 9: Sex: male Ethnicity/Population group: European Observation 10: Sex: male Ethnicity/Population group: European Observation 11: Sex: female Ethnicity/Population group: European Observation 12: Sex: male Ethnicity/Population group: European
Pathogenic (Feb 01, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Abnormal bleeding Affected status: yes Allele origin: unknown	NIHR Bioresource Rare Diseases, University of Cambridge Study: ThromboGenomics Accession: SCV000899410.1 First in ClinVar: Sep 29, 2019 Last updated: Sep 29, 2019	Publications: PubMed (1) PubMed: 31064749 Sex: female Ethnicity/Population group: European
Pathogenic (Apr 20, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial visceral amyloidosis, Ostertag type Congenital afibrinogenemia Familial dysfibrinogenemia Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002804033.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Apr 09, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001874102.6 First in ClinVar: Sep 19, 2021 Last updated: Sep 29, 2024	Comment: Published functional studies suggest a damaging effect: impaired thrombin polymerization, reduced fibrinogen clottability, reduced fibrinolysis velocity, and delayed release of fibrinopeptide A (PMID: 6830702, 22967385, … (more) Published functional studies suggest a damaging effect: impaired thrombin polymerization, reduced fibrinogen clottability, reduced fibrinolysis velocity, and delayed release of fibrinopeptide A (PMID: 6830702, 22967385, 22880226); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); Also known as R16H using alternate nomenclature; This variant is associated with the following publications: (PMID: 32877852, 33822462, 33443927, 34275736, 32939696, 23962069, 22880226, 22967385, 6830702, 27684817, 6191801, 2738154, 9391726, 25320241, 26577257, 29070135, 29869737, 30856382, 31314131, 30332696, 32166693, 30349899, 2379562, 35949040, 35975558, 31064749, 3618591, 34455742, 7298640, 22169505) (less)
Pathogenic (Apr 08, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Familial dysfibrinogenemia Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002511863.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022	Publications: PubMed (4) PubMed: 3618591‚ 32166693‚ 33668986‚ 32877852 Comment: Variant summary: FGA c.104G>A (p.Arg35His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more) Variant summary: FGA c.104G>A (p.Arg35His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251286 control chromosomes (gnomAD). c.104G>A has been reported in the literature in multiple individuals affected with Congenital Dysfibrinogenemia (e.g. Simurda_2020, Szanto_2021, Zhou_2021), including at least one homozygote (Alving_1987). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and two as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Jul 11, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial dysfibrinogenemia Affected status: unknown Allele origin: germline	Johns Hopkins Genomics, Johns Hopkins University Accession: SCV002570398.1 First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022	Publications: PubMed (11) PubMed: 17982313‚ 22880226‚ 25816717‚ 27684817‚ 28101869‚ 30332696‚ 32877852‚ 3345340‚ 3590111‚ 3618591‚ 4052020 Comment: This FGA missense variant has been identified in the heterozygous state in multiple individuals with congenital dysfibrinogenemia, and is also reported in individuals with FGA-related … (more) This FGA missense variant has been identified in the heterozygous state in multiple individuals with congenital dysfibrinogenemia, and is also reported in individuals with FGA-related congenital fibrinogen defects due to biallelic variants. This variant (rs121909607) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 4/282670 total alleles; 0.0014%; no homozygotes). It has been reported in ClinVar7 (Variation ID 16404). Three bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is evolutionarily conserved across all species assessed. Functional studies support that this missense change impacts protein function. We consider c.104G>A in FGA to be pathogenic. (less)
Pathogenic (Aug 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial dysfibrinogenemia Affected status: yes Allele origin: germline	Genetics and Molecular Pathology, SA Pathology Additional submitter: Shariant Australia, Australian Genomics Accession: SCV004175401.1 First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023	Publications: PubMed (2) PubMed: 31064749‚ 34275736 Comment: The FGA c.104G>A variant is classified as Pathogenic (PS1, PS4, PM1, PM2) The FGA c.104G>A variant is a single nucleotide change in exon 2/6 of … (more) The FGA c.104G>A variant is classified as Pathogenic (PS1, PS4, PM1, PM2) The FGA c.104G>A variant is a single nucleotide change in exon 2/6 of the FGA gene, which is predicted to change the amino acid arginine at position 35 in the protein to histidine. The variant has been reported in probands with a clinical presentation of MIM: 616004 (PS4). The variant is rare in population databases (gnomAD allele frequency = 0.0013%; 2 het and 0 hom in 152172 sequenced alleles; highest frequency = 0.0024%, African/African American population) (PM2). Detected in 7x patients with disease in PMID 31064749. This variant is located in a conserved region (PM1). (PMID:34275736) This variant results in the same amino acid change as a previously established variant (PS1). The variant has been reported in dbSNP (rs121909607) and has been reported as Pathogenic/Likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 16404). It has not been reported in HGMD. (less)
Pathogenic (Jan 04, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV001715840.3 First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024	Comment: PM1, PM2, PM5, PS3, PS4_moderate Number of individuals with the variant: 17
Pathogenic (Jul 01, 1989)	no assertion criteria provided Method: literature only	FIBRINOGEN PETOSKEY Affected status: not provided Allele origin: germline	OMIM Accession: SCV000038124.5 First in ClinVar: Apr 04, 2013 Last updated: Nov 09, 2018	Publications: PubMed (7) PubMed: 7298640‚ 6191801‚ 4052020‚ 3618591‚ 3590111‚ 2738154‚ 3345340 Qureshi, G. D., Evans, H. J., (more...) Qureshi, G. D., Evans, H. J., Vennart, R. M., Magnant, J. P., Sabau, J. M., Willoughby, J. B., Koehn, J. A. Fibrinogen White Marsh--a new human fibrinogen variant with alpha chain defect. (Abstract) Clin. Res. 31: 321A-only, 1983. Ebert, R. F. Index of Variant Human (more...) Ebert, R. F. Index of Variant Human Fibrinogens. Rockville, Md.: Privately published (pub.) 1990. Galanakis, D. K., Henschen, A., (more...) Galanakis, D. K., Henschen, A., Keeling, M., Kehl, M., Dismore, R., Peerschke, E. I. Fibrinogen Louisville: an A-alpha-16-arg-to-his defect that forms no hybrid molecules in heterozygous individuals and inhibits aggregation of normal fibrin monomers. Ann. N.Y. Acad. Sci. 408: 644-648, 1983. Comment on evidence: Fibrinogen Petoskey-1 has also been called fibrinogen Amiens-1, Amiens-2, Bergamo-3, Bern-2, Bicetre-1, Birmingham-1, Chapel Hill-2, Clermont-Ferrand-1, Giessen-1, Leitchfield, Long Beach-1, Louisville-1, Manchester-1, Paris-6, Petoskey-1, Seattle-2, … (more) Fibrinogen Petoskey-1 has also been called fibrinogen Amiens-1, Amiens-2, Bergamo-3, Bern-2, Bicetre-1, Birmingham-1, Chapel Hill-2, Clermont-Ferrand-1, Giessen-1, Leitchfield, Long Beach-1, Louisville-1, Manchester-1, Paris-6, Petoskey-1, Seattle-2, Sheffield-2, Sydney-1, Sydney-2, and White Marsh-1. In fibrinogen Petoskey (named for Petoskey, Michigan, the site of the hospital where the blood samples were collected), Higgins and Shafer (1981) detected replacement of arg-A(alpha)16 by a histidyl residue (R16H). In an abnormal fibrinogen associated with excessive postpartum bleeding and called fibrinogen White Marsh for the Virginia town of the patient's residence, Qureshi et al. (1983) also found the R16H mutation in the alpha chain. Carrell et al. (1983) gave the name fibrinogen Chapel Hill to a fibrinogen variant associated with thrombotic disease. Fibrinogen Manchester also exhibits the R16H mutation. Southan et al. (1985) found that platelet fibrinogen expresses the heterozygous R16H phenotype, thus supporting the view that the A-alpha chains of platelet and plasma fibrinogen are produced by a single genetic locus. Alving and Henschen (1987) reported that a patient homozygous for fibrinogen Giessen I had a substitution of histidine for arginine at position 16. Although this patient had had excessive postpartum bleeding, she had normal hemostasis throughout several minor surgical procedures and during hysterectomy. Reber et al. (1987) described 2 fibrinogen variants in which there was a substitution for arginine-16 in the alpha chain by histidine in one and by cysteine in the other; these were designated fibrinogen Bergamo III and fibrinogen Torino (134820.0003), respectively. See also Galanakis et al. (1983), Ebert et al. (1986), and Siebenlist et al. (1988). According to Galanakis (1993), the R16H mutation had been identified in 22 unrelated families, making it the most frequent form of dysfibrinogenemia. Together with R16C, it represented the majority of the mutations characterized, 37 out of 63. (less)
Pathogenic (May 28, 2024)	no assertion criteria provided Method: clinical testing	FGA-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004117662.3 First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024	Comment: The FGA c.104G>A variant is predicted to result in the amino acid substitution p.Arg35His. This variant, also referred to as p.Arg16His using legacy nomenclature, has … (more) The FGA c.104G>A variant is predicted to result in the amino acid substitution p.Arg35His. This variant, also referred to as p.Arg16His using legacy nomenclature, has been reported in many patients to be causative for autosomal dominant congenital dysfibrinogenemia (Casini et al. 2015. PubMed ID: 25320241; Siebenlist et al. 1988. PubMed ID: 3345340; Smith et al. 2018. PubMed ID: 30349899; Shapiro et al. 2013. PubMed ID: 23061815). Other missense variants affecting this amino acid (p.Arg35Cys, p.Arg35Ser, p.Arg35Pro) have also been reported in patients with dysfibrinogenemia, suggesting p.Arg35 is important for proper FGA protein function (Miesbach et al. 2010. PubMed ID: 19923982; Shapiro et al. 2013. PubMed ID: 23061815). This variant is reported in 0.0031% of alleles in individuals of European (non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. (less)

Comment:

Published functional studies suggest a damaging effect: impaired thrombin polymerization, reduced fibrinogen clottability, reduced fibrinolysis velocity, and delayed release of fibrinopeptide A (PMID: 6830702, 22967385, 22880226); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); Also known as R16H using alternate nomenclature; This variant is associated with the following publications: (PMID: 32877852, 33822462, 33443927, 34275736, 32939696, 23962069, 22880226, 22967385, 6830702, 27684817, 6191801, 2738154, 9391726, 25320241, 26577257, 29070135, 29869737, 30856382, 31314131, 30332696, 32166693, 30349899, 2379562, 35949040, 35975558, 31064749, 3618591, 34455742, 7298640, 22169505)

Comment:

Variant summary: FGA c.104G>A (p.Arg35His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251286 control chromosomes (gnomAD). c.104G>A has been reported in the literature in multiple individuals affected with Congenital Dysfibrinogenemia (e.g. Simurda_2020, Szanto_2021, Zhou_2021), including at least one homozygote (Alving_1987). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and two as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

This FGA missense variant has been identified in the heterozygous state in multiple individuals with congenital dysfibrinogenemia, and is also reported in individuals with FGA-related congenital fibrinogen defects due to biallelic variants. This variant (rs121909607) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 4/282670 total alleles; 0.0014%; no homozygotes). It has been reported in ClinVar7 (Variation ID 16404). Three bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is evolutionarily conserved across all species assessed. Functional studies support that this missense change impacts protein function. We consider c.104G>A in FGA to be pathogenic.

Comment:

The FGA c.104G>A variant is classified as Pathogenic (PS1, PS4, PM1, PM2) The FGA c.104G>A variant is a single nucleotide change in exon 2/6 of the FGA gene, which is predicted to change the amino acid arginine at position 35 in the protein to histidine. The variant has been reported in probands with a clinical presentation of MIM: 616004 (PS4). The variant is rare in population databases (gnomAD allele frequency = 0.0013%; 2 het and 0 hom in 152172 sequenced alleles; highest frequency = 0.0024%, African/African American population) (PM2). Detected in 7x patients with disease in PMID 31064749. This variant is located in a conserved region (PM1). (PMID:34275736) This variant results in the same amino acid change as a previously established variant (PS1). The variant has been reported in dbSNP (rs121909607) and has been reported as Pathogenic/Likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 16404). It has not been reported in HGMD.

Comment:

The FGA c.104G>A variant is predicted to result in the amino acid substitution p.Arg35His. This variant, also referred to as p.Arg16His using legacy nomenclature, has been reported in many patients to be causative for autosomal dominant congenital dysfibrinogenemia (Casini et al. 2015. PubMed ID: 25320241; Siebenlist et al. 1988. PubMed ID: 3345340; Smith et al. 2018. PubMed ID: 30349899; Shapiro et al. 2013. PubMed ID: 23061815). Other missense variants affecting this amino acid (p.Arg35Cys, p.Arg35Ser, p.Arg35Pro) have also been reported in patients with dysfibrinogenemia, suggesting p.Arg35 is important for proper FGA protein function (Miesbach et al. 2010. PubMed ID: 19923982; Shapiro et al. 2013. PubMed ID: 23061815). This variant is reported in 0.0031% of alleles in individuals of European (non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical and molecular characterization of Iranian patients with congenital fibrinogen disorders.	Mohsenian S	Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis	2021	PMID: 34275736
Whole Blood Thromboelastometry by ROTEM and Thrombin Generation by Genesia According to the Genotype and Clinical Phenotype in Congenital Fibrinogen Disorders.	Szanto T	International journal of molecular sciences	2021	PMID: 33668986
Identification and characterization of novel mutations in Chinese patients with congenital fibrinogen disorders.	Zhou P	Blood cells, molecules & diseases	2021	PMID: 32877852
Comparison of clinical phenotype with genetic and laboratory results in 31 patients with congenital dysfibrinogenemia in northern Slovakia.	Simurda T	International journal of hematology	2020	PMID: 32166693
Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.	Downes K	Blood	2019	PMID: 31064749
Mutational Epidemiology of Congenital Fibrinogen Disorders.	Casini A	Thrombosis and haemostasis	2018	PMID: 30332696
Fibrin Formation, Structure and Properties.	Weisel JW	Sub-cellular biochemistry	2017	PMID: 28101869
Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His.	Luo M	Medicine	2016	PMID: 27684817
Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management.	Casini A	Journal of thrombosis and haemostasis : JTH	2015	PMID: 25816717
[Functional analysis for dysfibrinogenemias, Toyama and Adachi, which have a mutation of Aalpha16Arg-->His (CGT-->CAT) with aberrant fibrinopeptide A release].	Soya K	Rinsho byori. The Japanese journal of clinical pathology	2012	PMID: 22880226
Homophenotypic Aalpha R16H fibrinogen (Kingsport): uniquely altered polymerization associated with slower fibrinopeptide A than fibrinopeptide B release.	Galanakis DK	Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis	2007	PMID: 17982313
Fibrinogen Stony Brook, a heterozygous A alpha 16Arg----Cys dysfibrinogenemia. Evaluation of diminished platelet aggregation support and of enhanced inhibition of fibrin assembly.	Galanakis DK	The Journal of clinical investigation	1989	PMID: 2738154
Fibrinogen Birmingham: a heterozygous dysfibrinogenemia (A alpha 16 Arg----His) containing heterodimeric molecules.	Siebenlist KR	Blood	1988	PMID: 3345340
Fibrinogen giessen I: a congenital homozygously expressed dysfibrinogenemia with A alpha 16 Arg----His substitution.	Alving BM	American journal of hematology	1987	PMID: 3618591
Fibrinogen Bergamo III and fibrinogen Torino: two further variants with hereditary molecular defects in fibrinopeptide A.	Reber P	Thrombosis research	1987	PMID: 3590111
Fibrinogen Manchester. Detection of a heterozygous phenotype in the intraplatelet pool.	Southan C	The Biochemical journal	1985	PMID: 4052020
Hereditary dysfibrinogenemia in a patient with thrombotic disease.	Carrell N	Blood	1983	PMID: 6191801
Fibrinogen Petoskey, a dysfibrinogenemia characterized by replacement of Arg-A alpha 16 by a histidyl residue. Evidence for thrombin-catalyzed hydrolysis at a histidyl residue.	Higgins DL	The Journal of biological chemistry	1981	PMID: 7298640
Ebert, R. F. Index of Variant Human Fibrinogens. Rockville, Md.: Privately published (pub.) 1990.	-	-	-	-
Galanakis, D. K., Henschen, A., Keeling, M., Kehl, M., Dismore, R., Peerschke, E. I. Fibrinogen Louisville: an A-alpha-16-arg-to-his defect that forms no hybrid molecules in heterozygous individuals and inhibits aggregation of normal fibrin monomers. Ann. N.Y. Acad. Sci. 408: 644-648, 1983.	-	-	-	-
Qureshi, G. D., Evans, H. J., Vennart, R. M., Magnant, J. P., Sabau, J. M., Willoughby, J. B., Koehn, J. A. Fibrinogen White Marsh--a new human fibrinogen variant with alpha chain defect. (Abstract) Clin. Res. 31: 321A-only, 1983.	-	-	-	-
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Text-mined citations for rs121909607 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_021871.4(FGA):c.104G>A (p.Arg35His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs121909607 ...