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NM_001354689.3(RAF1):c.781C>A (p.Pro261Thr)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 29, 2019
Accession:
VCV000040604.5
Variation ID:
40604
Description:
single nucleotide variant
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NM_001354689.3(RAF1):c.781C>A (p.Pro261Thr)

Allele ID
49074
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.2
Genomic location
3: 12604189 (GRCh38) GRCh38 UCSC
3: 12645688 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.11:g.12645688G>T
NC_000003.12:g.12604189G>T
NM_001354689.3:c.781C>A MANE Select NP_001341618.1:p.Pro261Thr missense
... more HGVS
Protein change
P261T, P147T, P180T, P228T
Other names
-
Canonical SPDI
NC_000003.12:12604188:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA250285
dbSNP: rs121434594
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Apr 15, 2011 RCV000037703.2
Pathogenic 2 criteria provided, single submitter Nov 29, 2019 RCV000149827.5
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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

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Apr 15, 2011)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000061365.6
Submitted: (Mar 21, 2019)
Evidence details
Comment:
The Pro261Thr variant has not been previously reported in the literature. This v ariant has been identified in one other proband with clinical features of … (more)
Pathogenic
(Nov 29, 2019)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000776868.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces proline with threonine at codon 261 of the RAF1 protein (p.Pro261Thr). The proline residue is highly conserved and there is a … (more)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Rasopathy
Allele origin: unknown
Baylor Genetics
Accession: SCV000196669.1
Submitted: (Sep 24, 2014)
Evidence details
Publications
PubMed (1)
Comment:
Variant classified using ACMG guidelines

Functional evidence

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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

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Title Author Journal Year Link
Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders. Xu S BMC medical genomics 2017 PMID: 29084544
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

Text-mined citations for rs121434594...

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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