VCV000016279.41 - ClinVar

NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)

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_023110.3(FGFR1):c.755C>G (p.Pro252Arg)

Variation ID: 16279 Accession: VCV000016279.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 8p11.23 8: 38424690 (GRCh38) [ NCBI UCSC ] 8: 38282208 (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	Aug 15, 2015	Oct 20, 2024	Mar 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_023110.3:c.755C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_075598.2:p.Pro252Arg	missense
NM_001174063.2:c.755C>G	NP_001167534.1:p.Pro252Arg	missense
NM_001174064.2:c.731C>G	NP_001167535.1:p.Pro244Arg	missense
NM_001174065.2:c.749C>G	NP_001167536.1:p.Pro250Arg	missense
NM_001174066.2:c.488C>G	NP_001167537.1:p.Pro163Arg	missense
NM_001174067.2:c.848C>G	NP_001167538.1:p.Pro283Arg	missense
NM_001354367.2:c.749C>G	NP_001341296.1:p.Pro250Arg	missense
NM_001354368.2:c.482C>G	NP_001341297.1:p.Pro161Arg	missense
NM_001354369.2:c.749C>G	NP_001341298.1:p.Pro250Arg	missense
NM_001354370.2:c.482C>G	NP_001341299.1:p.Pro161Arg	missense
NM_015850.4:c.749C>G	NP_056934.2:p.Pro250Arg	missense
NM_023105.3:c.488C>G	NP_075593.1:p.Pro163Arg	missense
NM_023106.3:c.482C>G	NP_075594.1:p.Pro161Arg	missense
NC_000008.11:g.38424690G>C
NC_000008.10:g.38282208G>C
NG_007729.1:g.49145C>G
LRG_993:g.49145C>G
LRG_993t1:c.755C>G	LRG_993p1:p.Pro252Arg
	P11362:p.Pro252Arg

... more HGVS ... less HGVS

Protein change

P252R, P244R, P250R, P283R, P161R, P163R

Other names

Canonical SPDI

NC_000008.11:38424689:G:C

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), exomes 0.00000

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

Links

ClinGen: CA280217 Genetic Testing Registry (GTR): GTR000504103 UniProtKB: P11362#VAR_004111 OMIM: 136350.0001 dbSNP: rs121909627 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.
FGFR1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	998	1128

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.
Jackson-Weiss syndrome	Pathogenic (2)	criteria provided, single submitter	Feb 2, 2022	RCV000017670.33
Pfeiffer syndrome	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Aug 27, 2021	RCV000017669.33
Hypogonadotropic hypogonadism 2 with or without anosmia Pfeiffer syndrome	Pathogenic (1)	criteria provided, single submitter	Mar 1, 2023	RCV000644520.10
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Mar 8, 2022	RCV001200303.25
Encephalocraniocutaneous lipomatosis Hartsfield-Bixler-Demyer syndrome Hypogonadotropic hypogonadism 2 with or without anosmia Jackson-Weiss syndrome Osteoglophonic dysplasia Pfeiffer syndrome Trigonocephaly 1	Pathogenic (1)	criteria provided, single submitter	Jul 17, 2021	RCV002496391.3

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 (Aug 27, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Pfeiffer syndrome Affected status: yes Allele origin: maternal	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology Study: CSER-SouthSeq Accession: SCV002012499.1 First in ClinVar: Nov 11, 2021 Last updated: Nov 11, 2021	Comment: ACMG codes: PS3; PS4; PM2; PP1; PP3; PP5 Number of individuals with the variant: 1 Clinical Features: Fetal growth restriction (present) , Small for gestational age (present) , Birth length less than 3rd percentile (present) , Micrognathia (present) , Abnormality of the … (more) Fetal growth restriction (present) , Small for gestational age (present) , Birth length less than 3rd percentile (present) , Micrognathia (present) , Abnormality of the face (present) , Stridor (present) , Epicanthus (present) , Low-set, posteriorly rotated ears (present) , Protruding ear (present) , Anteverted nares (present) , Depressed nasal bridge (present) , Hypoplasia of the maxilla (present) , Micrognathia (present) , Retrognathia (present) , 2-3 toe syndactyly (present) , Shallow orbits (present) , Malar flattening (present) (less)
Pathogenic (Jul 17, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pfeiffer syndrome Jackson-Weiss syndrome Hypogonadotropic hypogonadism 2 with or without anosmia Osteoglophonic dysplasia Trigonocephaly 1 Encephalocraniocutaneous lipomatosis Hartsfield-Bixler-Demyer syndrome Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002812328.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Mar 08, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV002319172.2 First in ClinVar: Apr 02, 2022 Last updated: Mar 04, 2023	Comment: Published functional studies demonstrate a damaging effect with a significantly increased bindings affinity for endogenous ligands; additionally functional studies in an animal model demonstrate a … (more) Published functional studies demonstrate a damaging effect with a significantly increased bindings affinity for endogenous ligands; additionally functional studies in an animal model demonstrate a damaging effect potentially via aberrant activation of downstream target Cbfa1 (Ibrahimi et al., 2004; Zhou et al., 2000); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23329143, 27065010, 7795583, 24127277, 10861678, 14564217, 7874169, 16957473, 24497711, 10942429, 31837199, 31016899, 32510873, 31167513, 32139749, 30207415, 34159400, 31785789, 14613973, 25251565) (less)
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pfeiffer syndrome Affected status: yes Allele origin: germline	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India Accession: SCV004030499.1 First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023
Pathogenic (Mar 01, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Pfeiffer syndrome Hypogonadotropic hypogonadism 2 with or without anosmia Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000766219.7 First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024	Publications: PubMed (11) PubMed: 28492532‚ 7795583‚ 7874169‚ 10861678‚ 14564217‚ 16957473‚ 24127277‚ 24497711‚ 25251565‚ 10942429‚ 14613973 Comment: For these reasons, this variant has been classified as Pathogenic. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic … (more) For these reasons, this variant has been classified as Pathogenic. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 252 of the FGFR1 protein (p.Pro252Arg). This variant is present in population databases (rs121909627, gnomAD 0.0009%). This missense change has been observed in individuals with Pfeiffer syndrome (PMID: 7795583, 7874169, 10861678, 14564217, 16957473, 24127277, 24497711, 25251565). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16279). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR1 protein function. Experimental studies have shown that this missense change affects FGFR1 function (PMID: 10942429, 14613973). (less)
Pathogenic (Feb 02, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Jackson-Weiss syndrome (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002768161.2 First in ClinVar: Dec 24, 2022 Last updated: Jul 23, 2024	Publications: PubMed (6) PubMed: 1456217‚ 18034870‚ 23812909‚ 24127277‚ 26942290‚ 31837199 Comment: Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function … (more) Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with FGFR1-related disease. Loss of function missense variants and variants predicted to undergo nonsense-mediated decay have been reported to cause Hartsfield syndrome (MIM#615465) and hypogonadotropic hypogonadism-2 [HH2] (MIM#147950). Gain of function missense variants have been reported to cause encephalocraniocutaneous lipomatosis, somatic mosaic (MIM#613001) and osteoglophonic dysplasia (MIM#166250). Additional missense variants have been reported in patients with Jackson-Weiss syndrome (MIM#123150), Pfeiffer syndrome (MIM#101600) or trigonocephaly 1 (MIM#190440) however, the mechanism of these variants is unknown (OMIM, PMID: 18034870, 23812909, 26942290). (I) 0107 - This gene is associated with autosomal dominant disease. Biallelic missense variants have been rarely reported in patients with Hartsfield syndrome (PMID: 23812909). (I) 0115 - Variants in this gene are known to have variable expressivity in patients with HH2 (PMID: 18034870). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to arginine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been observed in over ten individuals with FGFR1-related conditions. It has mainly been reported in individuals with Pfeiffer syndrome (MIM#101600) but has been observed in one individual with Jackson-Weiss syndrome (MIM#123150) (ClinVar, LOVD, DECIPHER, PMIDs: 24127277, 31837199, 1456217, 10861678). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
Pathogenic (Jun 01, 2020)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001371225.24 First in ClinVar: Jul 16, 2020 Last updated: Oct 20, 2024	Number of individuals with the variant: 1
Pathogenic (Jan 01, 2004)	no assertion criteria provided Method: literature only	JACKSON-WEISS SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037947.3 First in ClinVar: Apr 04, 2013 Last updated: Jun 14, 2019	Publications: PubMed (3) PubMed: 7874169‚ 10861678‚ 14613973 Comment on evidence: Pfeiffer Syndrome By SSCP analysis of FGFR1 in patients with Pfeiffer syndrome (101600), Muenke et al. (1994) found a C-to-G transversion at position 755 of … (more) Pfeiffer Syndrome By SSCP analysis of FGFR1 in patients with Pfeiffer syndrome (101600), Muenke et al. (1994) found a C-to-G transversion at position 755 of exon 5, predicting a pro252-to-arg substitution located between the second and third putative Ig domain of the FGFR1 protein. Proline residue is highly conserved in evolution, being present in chicken, mouse, rat, and all 4 human FGFR genes. Jackson-Weiss Syndrome Roscioli et al. (2000) reported the case of a patient with the skeletal findings of Jackson-Weiss syndrome (JWS; 123150) who manifested only mild craniofacial anomalies. They demonstrated heterozygosity for the P252R missense mutation in the FGFR1 gene. Variant Function By surface plasmon resonance analysis and X-ray crystallography, Ibrahimi et al. (2004) characterized the effects of proline-to-arginine mutations in FGFR1c and FGFR3c on ligand binding. Both the FGFR1c P252R mutation and the FGFR3c P250R (134934.0014) mutation exhibited an enhancement in ligand binding in comparison to their respective wildtype receptors. Binding of both mutant receptors to FGF9 (600921) was notably enhanced and implicated FGF9 as a potential pathophysiologic ligand for mutant FGFRs in mediating craniosynostosis. The crystal structure of the P252R mutant in complex with FGF2 showed that enhanced ligand binding was due to an additional set of receptor-ligand hydrogen bonds, similar to the gain-of-function interactions that occur in the crystal structure of the FGFR2c P253R (176943.0011) mutant in complex with FGF2. However, unlike the P253R mutant, neither the FGFR1c P252R mutant nor the FRGR3c P250R mutant bound appreciably to FGF7 (148180) or FGF10 (602115). Ibrahimi et al. (2004) suggested that this might explain why limb phenotypes observed in type I Pfeiffer syndrome (101600) and Muenke syndrome (602849) are less severe than limb abnormalities observed in Apert syndrome (101200). (less)
Pathogenic (Jan 01, 2004)	no assertion criteria provided Method: literature only	PFEIFFER SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037946.3 First in ClinVar: Apr 04, 2013 Last updated: Jun 14, 2019	Publications: PubMed (3) PubMed: 7874169‚ 10861678‚ 14613973 Comment on evidence: Pfeiffer Syndrome By SSCP analysis of FGFR1 in patients with Pfeiffer syndrome (101600), Muenke et al. (1994) found a C-to-G transversion at position 755 of … (more) Pfeiffer Syndrome By SSCP analysis of FGFR1 in patients with Pfeiffer syndrome (101600), Muenke et al. (1994) found a C-to-G transversion at position 755 of exon 5, predicting a pro252-to-arg substitution located between the second and third putative Ig domain of the FGFR1 protein. Proline residue is highly conserved in evolution, being present in chicken, mouse, rat, and all 4 human FGFR genes. Jackson-Weiss Syndrome Roscioli et al. (2000) reported the case of a patient with the skeletal findings of Jackson-Weiss syndrome (JWS; 123150) who manifested only mild craniofacial anomalies. They demonstrated heterozygosity for the P252R missense mutation in the FGFR1 gene. Variant Function By surface plasmon resonance analysis and X-ray crystallography, Ibrahimi et al. (2004) characterized the effects of proline-to-arginine mutations in FGFR1c and FGFR3c on ligand binding. Both the FGFR1c P252R mutation and the FGFR3c P250R (134934.0014) mutation exhibited an enhancement in ligand binding in comparison to their respective wildtype receptors. Binding of both mutant receptors to FGF9 (600921) was notably enhanced and implicated FGF9 as a potential pathophysiologic ligand for mutant FGFRs in mediating craniosynostosis. The crystal structure of the P252R mutant in complex with FGF2 showed that enhanced ligand binding was due to an additional set of receptor-ligand hydrogen bonds, similar to the gain-of-function interactions that occur in the crystal structure of the FGFR2c P253R (176943.0011) mutant in complex with FGF2. However, unlike the P253R mutant, neither the FGFR1c P252R mutant nor the FRGR3c P250R mutant bound appreciably to FGF7 (148180) or FGF10 (602115). Ibrahimi et al. (2004) suggested that this might explain why limb phenotypes observed in type I Pfeiffer syndrome (101600) and Muenke syndrome (602849) are less severe than limb abnormalities observed in Apert syndrome (101200). (less)
Pathogenic (Jun 17, 2021)	no assertion criteria provided Method: clinical testing	Pfeiffer syndrome Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, University Hospital Schleswig-Holstein Accession: SCV002011764.1 First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021

Comment:

Published functional studies demonstrate a damaging effect with a significantly increased bindings affinity for endogenous ligands; additionally functional studies in an animal model demonstrate a damaging effect potentially via aberrant activation of downstream target Cbfa1 (Ibrahimi et al., 2004; Zhou et al., 2000); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23329143, 27065010, 7795583, 24127277, 10861678, 14564217, 7874169, 16957473, 24497711, 10942429, 31837199, 31016899, 32510873, 31167513, 32139749, 30207415, 34159400, 31785789, 14613973, 25251565)

Comment:

For these reasons, this variant has been classified as Pathogenic. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 252 of the FGFR1 protein (p.Pro252Arg). This variant is present in population databases (rs121909627, gnomAD 0.0009%). This missense change has been observed in individuals with Pfeiffer syndrome (PMID: 7795583, 7874169, 10861678, 14564217, 16957473, 24127277, 24497711, 25251565). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16279). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR1 protein function. Experimental studies have shown that this missense change affects FGFR1 function (PMID: 10942429, 14613973).

Comment:

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with FGFR1-related disease. Loss of function missense variants and variants predicted to undergo nonsense-mediated decay have been reported to cause Hartsfield syndrome (MIM#615465) and hypogonadotropic hypogonadism-2 [HH2] (MIM#147950). Gain of function missense variants have been reported to cause encephalocraniocutaneous lipomatosis, somatic mosaic (MIM#613001) and osteoglophonic dysplasia (MIM#166250). Additional missense variants have been reported in patients with Jackson-Weiss syndrome (MIM#123150), Pfeiffer syndrome (MIM#101600) or trigonocephaly 1 (MIM#190440) however, the mechanism of these variants is unknown (OMIM, PMID: 18034870, 23812909, 26942290). (I) 0107 - This gene is associated with autosomal dominant disease. Biallelic missense variants have been rarely reported in patients with Hartsfield syndrome (PMID: 23812909). (I) 0115 - Variants in this gene are known to have variable expressivity in patients with HH2 (PMID: 18034870). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to arginine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been observed in over ten individuals with FGFR1-related conditions. It has mainly been reported in individuals with Pfeiffer syndrome (MIM#101600) but has been observed in one individual with Jackson-Weiss syndrome (MIM#123150) (ClinVar, LOVD, DECIPHER, PMIDs: 24127277, 31837199, 1456217, 10861678). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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
NGS targeted screening of 100 Scandinavian patients with coronal synostosis.	Topa A	American journal of medical genetics. Part A	2020	PMID: 31837199
Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis.	Bennett JT	American journal of human genetics	2016	PMID: 26942290
Variable expressivity of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation.	Bessenyei B	American journal of medical genetics. Part A	2014	PMID: 25251565
Mutational identification of fibroblast growth factor receptor 1 and fibroblast growth factor receptor 2 genes in craniosynostosis in Indian population.	Pandey RK	Indian journal of human genetics	2013	PMID: 24497711
Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.	Roscioli T	American journal of medical genetics. Part C, Seminars in medical genetics	2013	PMID: 24127277
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly.	Simonis N	Journal of medical genetics	2013	PMID: 23812909
Diversity in fibroblast growth factor receptor 1 regulation: learning from the investigation of Kallmann syndrome.	Kim SH	Journal of neuroendocrinology	2008	PMID: 18034870
FGFR1 Pfeiffer syndrome without craniosynostosis: an additional case report.	Hackett A	Clinical dysmorphology	2006	PMID: 16957473
Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.	Ibrahimi OA	Human molecular genetics	2004	PMID: 14613973
The appearance of the feet in Pfeiffer syndrome caused by FGFR1 P252R mutation.	Rossi M	Clinical dysmorphology	2003	PMID: 14564217
A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures.	Zhou YX	Human molecular genetics	2000	PMID: 10942429
Clinical findings in a patient with FGFR1 P252R mutation and comparison with the literature.	Roscioli T	American journal of medical genetics	2000	PMID: 10861678
Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.	Schell U	Human molecular genetics	1995	PMID: 7795583
A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.	Muenke M	Nature genetics	1994	PMID: 7874169
An evaluation of the nasolabial angle and the relative inclinations of the nose and upper lip.	Fitzgerald JP	American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics	1992	PMID: 1456217
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Text-mined citations for rs121909627 ...

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Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs121909627 ...