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NM_001354689.3(RAF1):c.1532C>G (p.Thr511Arg)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 6, 2019
Accession:
VCV000013959.3
Variation ID:
13959
Description:
single nucleotide variant
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NM_001354689.3(RAF1):c.1532C>G (p.Thr511Arg)

Allele ID
28998
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p25.2
Genomic location
3: 12585745 (GRCh38) GRCh38 UCSC
3: 12627244 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P04049:p.Thr491Arg
LRG_413:g.83435C>G
LRG_413t2:c.1532C>G LRG_413p2:p.Thr511Arg
... more HGVS
Protein change
T491R, T430R, T458R, T410R, T511R, T377R
Other names
-
Canonical SPDI
NC_000003.12:12585744:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA257064
UniProtKB: P04049#VAR_037819
OMIM: 164760.0003
dbSNP: rs80338799
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Jun 18, 2018 RCV000680803.1
Uncertain significance 1 criteria provided, single submitter Sep 6, 2019 RCV001229313.2
Pathogenic 1 no assertion criteria provided Aug 1, 2007 RCV000014988.25
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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
Likely pathogenic
(Jun 18, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000808247.1
Submitted: (Sep 14, 2018)
Evidence details
Comment:
The T491R variant has been published previously in association with Noonan syndrome (Pandit et al., 2007). The variant is not observed in large population cohorts … (more)
Uncertain significance
(Sep 06, 2019)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV001401755.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces threonine with arginine at codon 491 of the RAF1 protein (p.Thr491Arg). The threonine residue is highly conserved and there is a … (more)
Pathogenic
(Aug 01, 2007)
no assertion criteria provided
Method: literature only
NOONAN SYNDROME 5
Allele origin: germline
OMIM
Accession: SCV000035244.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)

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
RAF1-associated Noonan syndrome presenting antenatally with an abnormality of skull shape, subdural haematoma and associated with novel cerebral malformations. Hartill VL Clinical dysmorphology 2017 PMID: 27753652
Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants. Wu X Molecular and cellular biology 2012 PMID: 22826437
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Pandit B Nature genetics 2007 PMID: 17603483

Text-mined citations for rs80338799...

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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 Oct 24, 2021