NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jul 3, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe)]

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

BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe)
Other names:
p.L245F:TTA>TTC; NM_004333.4(BRAF):c.735A>C
  • NC_000007.14:g.140801537T>G
  • NG_007873.3:g.128228A>C
  • NM_001354609.2:c.735A>C
  • NM_001374244.1:c.735A>C
  • NM_001374258.1:c.735A>CMANE SELECT
  • NM_001378467.1:c.744A>C
  • NM_001378468.1:c.735A>C
  • NM_001378469.1:c.735A>C
  • NM_001378470.1:c.633A>C
  • NM_001378471.1:c.735A>C
  • NM_001378472.1:c.579A>C
  • NM_001378473.1:c.579A>C
  • NM_001378474.1:c.735A>C
  • NM_001378475.1:c.471A>C
  • NM_004333.6:c.735A>C
  • NP_001341538.1:p.Leu245Phe
  • NP_001361173.1:p.Leu245Phe
  • NP_001361187.1:p.Leu245Phe
  • NP_001365396.1:p.Leu248Phe
  • NP_001365397.1:p.Leu245Phe
  • NP_001365398.1:p.Leu245Phe
  • NP_001365399.1:p.Leu211Phe
  • NP_001365400.1:p.Leu245Phe
  • NP_001365401.1:p.Leu193Phe
  • NP_001365402.1:p.Leu193Phe
  • NP_001365403.1:p.Leu245Phe
  • NP_001365404.1:p.Leu157Phe
  • NP_004324.2:p.Leu245Phe
  • LRG_299t1:c.735A>C
  • LRG_299:g.128228A>C
  • NC_000007.13:g.140501337T>G
  • NM_004333.4:c.735A>C
  • P15056:p.Leu245Phe
  • c.735A>C
Protein change:
L157F; LEU245PHE
UniProtKB: P15056#VAR_058623; OMIM: 164757.0027; dbSNP: rs397507466
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001354609.2:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374244.1:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374258.1:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378467.1:c.744A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378468.1:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378469.1:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378470.1:c.633A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378471.1:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378472.1:c.579A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378473.1:c.579A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378474.1:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378475.1:c.471A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004333.6:c.735A>C - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000057188GeneDxcriteria provided, single submitter
(Jul 3, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000057188.16

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


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 et al., 2009). It has also been confirmed to occur de novo in an individual sent to GeneDx for testing. The variant is not observed in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. A different nucleotide change leading to the same missense variant (c.735 A>T) as well as missense variants in nearby residues (T241P/R/M, T244P, A246P) have been reported in the Human Gene Mutation Database in association with cardio-facio-cutaneous syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, we consider the variant to be pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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