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NM_004333.6(BRAF):c.1455G>T (p.Leu485Phe) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 21, 2014
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000844617.4

Allele description [Variation Report for NM_004333.6(BRAF):c.1455G>T (p.Leu485Phe)]

NM_004333.6(BRAF):c.1455G>T (p.Leu485Phe)

Gene:
BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q34
Genomic location:
Preferred name:
NM_004333.6(BRAF):c.1455G>T (p.Leu485Phe)
HGVS:
  • NC_000007.14:g.140778053C>A
  • NG_007873.3:g.151712G>T
  • NM_001354609.2:c.1455G>T
  • NM_001374244.1:c.1575G>T
  • NM_001374258.1:c.1575G>T
  • NM_001378467.1:c.1464G>T
  • NM_001378468.1:c.1455G>T
  • NM_001378469.1:c.1389G>T
  • NM_001378470.1:c.1353G>T
  • NM_001378471.1:c.1344G>T
  • NM_001378472.1:c.1299G>T
  • NM_001378473.1:c.1299G>T
  • NM_001378474.1:c.1455G>T
  • NM_001378475.1:c.1191G>T
  • NM_004333.6:c.1455G>TMANE SELECT
  • NP_001341538.1:p.Leu485Phe
  • NP_001361173.1:p.Leu525Phe
  • NP_001361187.1:p.Leu525Phe
  • NP_001365396.1:p.Leu488Phe
  • NP_001365397.1:p.Leu485Phe
  • NP_001365398.1:p.Leu463Phe
  • NP_001365399.1:p.Leu451Phe
  • NP_001365400.1:p.Leu448Phe
  • NP_001365401.1:p.Leu433Phe
  • NP_001365402.1:p.Leu433Phe
  • NP_001365403.1:p.Leu485Phe
  • NP_001365404.1:p.Leu397Phe
  • NP_004324.2:p.Leu485Phe
  • LRG_299t1:c.1455G>T
  • LRG_299:g.151712G>T
  • NC_000007.13:g.140477853C>A
  • NM_004333.4:c.1455G>T
  • NM_004333.6(BRAF):c.1455G>TMANE SELECT
  • P15056:p.Leu485Phe
Protein change:
L397F
Links:
UniProtKB: P15056#VAR_026115; dbSNP: rs180177036
NCBI 1000 Genomes Browser:
rs180177036
Molecular consequence:
  • NM_001354609.2:c.1455G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374244.1:c.1575G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374258.1:c.1575G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378467.1:c.1464G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378468.1:c.1455G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378469.1:c.1389G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378470.1:c.1353G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378471.1:c.1344G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378472.1:c.1299G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378473.1:c.1299G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378474.1:c.1455G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378475.1:c.1191G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004333.6:c.1455G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Noonan syndrome (NS)
Synonyms:
Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:
MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950
Name:
Cardio-facio-cutaneous syndrome
Synonyms:
Cardiofaciocutaneous syndrome; CFC syndrome
Identifiers:
MONDO: MONDO:0015280; MedGen: C1275081; Orphanet: 1340; OMIM: PS115150

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000204150Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Oct 21, 2014) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS, McCormick F, Rauen KA.

Science. 2006 Mar 3;311(5765):1287-90. Epub 2006 Jan 26.

PubMed [citation]
PMID:
16439621

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.

Niihori T, Aoki Y, Narumi Y, Neri G, Cavé H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, et al.

Nat Genet. 2006 Mar;38(3):294-6. Epub 2006 Feb 12.

PubMed [citation]
PMID:
16474404
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204150.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The c.1455G>T (Leu485Phe) variant in BRAF has been previously identified in one individual with clinical features of a Cardio-facio-cutaneous syndrome (LMM unpu blished data). It was absent from large population studies (http://evs.gs.washin gton.edu/EVS/). In addition, a different variant with the same amino acid change (c.1455G>C) was identified in four individuals with clinical features of a RASo pathy (Niihori 2006, Rodriguez-Viciana 2006, LMM unpublished data). In vitro fu nctional studies provide some evidence that the Leu485Phe variant may impact pro tein function by increasing its kinase activity (Rodriguez-Viciana 2008). Howeve r, these types of assays may not accurately represent biological function. In s ummary, this variant meets our criteria to be classified as pathogenic (http://p cpgmwww.partners.org/personalizedmedicince/LMM).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Sep 29, 2024