Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_001354689.3(RAF1):c.782C>G (p.Pro261Arg)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Mar 21, 2019)
Last evaluated:
Feb 16, 2018
Accession:
VCV000040606.3
Variation ID:
40606
Description:
single nucleotide variant
Help

NM_001354689.3(RAF1):c.782C>G (p.Pro261Arg)

Allele ID
49076
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.2
Genomic location
3: 12604188 (GRCh38) GRCh38 UCSC
3: 12645687 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.12:g.12604188G>C
NC_000003.11:g.12645687G>C
NM_001354689.3:c.782C>G MANE Select NP_001341618.1:p.Pro261Arg missense
... more HGVS
Protein change
P261R, P147R, P180R, P228R
Other names
p.P261R:CCT>CGT
Canonical SPDI
NC_000003.12:12604187:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA134753
dbSNP: rs397516828
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jul 14, 2015 RCV000159077.2
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Feb 16, 2018 RCV000590070.2
Pathogenic 1 criteria provided, single submitter Feb 17, 2016 RCV000037706.4
Pathogenic 1 no assertion criteria provided Nov 18, 2018 RCV000277865.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RAF1 No evidence available No evidence available GRCh38
GRCh37
566 619

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jul 10, 2017)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698127.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: The RAF1 c.782C>G (p.Pro261Arg) variant involves the alteration of a highly conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this … (more)
Pathogenic
(Jul 14, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000333074.4
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (3)
Other databases
http://www.egl-eurofins.com/emvc…
http://www.pagepress.org/journal…
Pathogenic
(Feb 16, 2018)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000829989.1
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces proline with arginine at codon 261 of the RAF1 protein (p.Pro261Arg). The proline residue is highly conserved and there is a … (more)
Pathogenic
(Jan 10, 2014)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000209020.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The P261R missense mutation was identified in the RAF1 gene. It has not been published as a pathogenic variant or benign polymorphism, to our knowledge. … (more)
Pathogenic
(Feb 17, 2016)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000061368.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (2)
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Pathogenic
(Nov 18, 2018)
no assertion criteria provided
Method: clinical testing
Noonan syndrome 5
Allele origin: germline
Baylor Genetics
Accession: SCV000854623.1
Submitted: (Nov 23, 2018)
Evidence details

Functional evidence

Help
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.

Citations for this variant

Help
Title Author Journal Year Link
RAF1 variants causing biventricular hypertrophic cardiomyopathy in two preterm infants: further phenotypic delineation and review of literature. Thompson D Clinical dysmorphology 2017 PMID: 28777121
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
A Novel Noonan Syndrome RAF1 Mutation: Lethal Course in a Preterm Infant. Ratola A Pediatric reports 2015 PMID: 26266034
External ear anomalies and hearing impairment in Noonan Syndrome. van Trier DC International journal of pediatric otorhinolaryngology 2015 PMID: 25862627
Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Wang P Oncogene 2013 PMID: 22824796
Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy. Ezquieta B Revista espanola de cardiologia (English ed.) 2012 PMID: 22465605
Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. Lee BH The Journal of pediatrics 2011 PMID: 21784453
Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations. Longoni M American journal of medical genetics. Part A 2010 PMID: 20683980
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Pandit B Nature genetics 2007 PMID: 17603483
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Razzaque MA Nature genetics 2007 PMID: 17603482
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RAF1 - - - -
http://www.pagepress.org/journals/index.php/pr/article/view/5955/4692 - - - -

Text-mined citations for rs397516828...

Help
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 Jul 07, 2021