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NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
8 (Most recent: Nov 19, 2021)
Last evaluated:
May 10, 2019
Accession:
VCV000040347.8
Variation ID:
40347
Description:
single nucleotide variant
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NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe)

Allele ID
48817
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q34
Genomic location
7: 140801537 (GRCh38) GRCh38 UCSC
7: 140501337 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P15056:p.Leu245Phe
NC_000007.13:g.140501337T>G
NC_000007.14:g.140801537T>G
... more HGVS
Protein change
L245F, L211F, L157F, L248F, L193F
Other names
p.L245F:TTA>TTC
NM_004333.4(BRAF):c.735A>C
Canonical SPDI
NC_000007.14:140801536:T:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA280027
UniProtKB: P15056#VAR_058623
OMIM: 164757.0027
dbSNP: rs397507466
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 reviewed by expert panel May 10, 2019 RCV000788013.1
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 28, 2020 RCV000037956.3
Pathogenic 2 criteria provided, single submitter Jul 3, 2018 RCV000033283.7
Pathogenic 1 criteria provided, single submitter Dec 31, 2019 RCV000469440.3
Likely pathogenic 1 criteria provided, single submitter May 18, 2017 RCV000515291.1
Pathogenic 1 no assertion criteria provided Sep 1, 2009 RCV000171142.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRAF Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
570 613

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(May 10, 2019)
reviewed by expert panel
Method: curation
Noonan syndrome and Noonan-related syndrome
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen RASopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000927045.1
Submitted: (Jul 15, 2019)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
The c.735A>C (p.Leu245Phe) variant in BRAF has been reported as a a de novo occurrence, one of which was confirmed in at least 4 patients … (more)
Pathogenic
(Dec 28, 2020)
criteria provided, single submitter
Method: clinical testing
Cardio-facio-cutaneous syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001467792.1
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: BRAF c.735A>C (p.Leu245Phe) results in a non-conservative amino acid change located in the phorbol ester/diacylglycerol-binding domain (IPR002219) of the encoded protein sequence. Five … (more)
Pathogenic
(Dec 31, 2019)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000553831.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces leucine with phenylalanine at codon 245 of the BRAF protein (p.Leu245Phe). The leucine residue is highly conserved and there is a … (more)
Likely pathogenic
(May 18, 2017)
criteria provided, single submitter
Method: clinical testing
Cardiofaciocutaneous syndrome 1
Noonan syndrome 1
Lung cancer
Noonan syndrome 7
LEOPARD syndrome 3
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000611176.1
Submitted: (May 23, 2017)
Evidence details
Pathogenic
(Jul 03, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000057188.16
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The L245F variant has been published previously in association with Noonan spectrum disorders, including as an apparently de novo occurrence (Koudova et al., 2009; Sarkozy … (more)
Likely pathogenic
(Jun 24, 2010)
criteria provided, single submitter
Method: clinical testing
Cardio-facio-cutaneous syndrome
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000061622.5
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (2)
Pathogenic
(Sep 01, 2009)
no assertion criteria provided
Method: literature only
LEOPARD SYNDROME 3
Allele origin: germline
OMIM
Accession: SCV000223706.2
Submitted: (May 27, 2015)
Evidence details
Publications
PubMed (1)
Pathogenic
(May 06, 2020)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002022636.1
Submitted: (Nov 19, 2021)
Evidence details

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
Clinical and molecular characterization of children with Noonan syndrome and other RASopathies in Argentina. Chinton J Archivos argentinos de pediatria 2019 PMID: 31560489
Diagnostic Yield of Intellectual Disability Gene Panels. Pekeles H Pediatric neurology 2019 PMID: 30581057
Genetic diagnosis of neurofibromatosis type 1: targeted next- generation sequencing with Multiple Ligation-Dependent Probe Amplification analysis. Wu-Chou YH Journal of biomedical science 2018 PMID: 30290804
RASopathies: Clinical Diagnosis in the First Year of Life. Digilio MC Molecular syndromology 2011 PMID: 22190897
Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence. Koudova M European journal of medical genetics 2009 PMID: 19416762
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Sarkozy A Human mutation 2009 PMID: 19206169
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/cf6b44e4-40ca-4713-b35e-0ad194eb2f96 - - - -

Text-mined citations for rs397507466...

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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 Nov 28, 2021