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NM_001374258.1(BRAF):c.2034T>G (p.Asp678Glu) AND Cardio-facio-cutaneous syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Mar 14, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000150199.6

Allele description [Variation Report for NM_001374258.1(BRAF):c.2034T>G (p.Asp678Glu)]

NM_001374258.1(BRAF):c.2034T>G (p.Asp678Glu)

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_001374258.1(BRAF):c.2034T>G (p.Asp678Glu)
Other names:
p.D638E:GAT>GAG
HGVS:
  • NC_000007.14:g.140749365A>C
  • NG_007873.3:g.180400T>G
  • NM_001354609.2:c.1914T>G
  • NM_001374244.1:c.2034T>G
  • NM_001374258.1:c.2034T>G
  • NM_001378467.1:c.1923T>G
  • NM_001378468.1:c.1914T>G
  • NM_001378469.1:c.1848T>G
  • NM_001378470.1:c.1812T>G
  • NM_001378471.1:c.1803T>G
  • NM_001378472.1:c.1758T>G
  • NM_001378473.1:c.1758T>G
  • NM_001378474.1:c.1914T>G
  • NM_001378475.1:c.1650T>G
  • NM_004333.6:c.1914T>GMANE SELECT
  • NP_001341538.1:p.Asp638Glu
  • NP_001361173.1:p.Asp678Glu
  • NP_001361187.1:p.Asp678Glu
  • NP_001365396.1:p.Asp641Glu
  • NP_001365397.1:p.Asp638Glu
  • NP_001365398.1:p.Asp616Glu
  • NP_001365399.1:p.Asp604Glu
  • NP_001365400.1:p.Asp601Glu
  • NP_001365401.1:p.Asp586Glu
  • NP_001365402.1:p.Asp586Glu
  • NP_001365403.1:p.Asp638Glu
  • NP_001365404.1:p.Asp550Glu
  • NP_004324.2:p.Asp638Glu
  • LRG_299t1:c.1914T>G
  • LRG_299:g.180400T>G
  • NC_000007.13:g.140449165A>C
  • NM_004333.4:c.1914T>G
  • NM_004333.5:c.1914T>G
  • P15056:p.Asp638Glu
Protein change:
D550E
Links:
UniProtKB: P15056#VAR_058630; dbSNP: rs180177042
NCBI 1000 Genomes Browser:
rs180177042
Molecular consequence:
  • NM_001354609.2:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374244.1:c.2034T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374258.1:c.2034T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378467.1:c.1923T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378468.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378469.1:c.1848T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378470.1:c.1812T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378471.1:c.1803T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378472.1:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378473.1:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378474.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378475.1:c.1650T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004333.6:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000197128Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Pathogenic
(Aug 27, 2013)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV005016614Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 14, 2024)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome.

Rodriguez-Viciana P, Rauen KA.

Methods Enzymol. 2008;438:277-89. doi: 10.1016/S0076-6879(07)38019-1.

PubMed [citation]
PMID:
18413255

Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum.

Sarkozy A, Carta C, Moretti S, Zampino G, Digilio MC, Pantaleoni F, Scioletti AP, Esposito G, Cordeddu V, Lepri F, Petrangeli V, Dentici ML, Mancini GM, Selicorni A, Rossi C, Mazzanti L, Marino B, Ferrero GB, Silengo MC, Memo L, Stanzial F, Faravelli F, et al.

Hum Mutat. 2009 Apr;30(4):695-702. doi: 10.1002/humu.20955.

PubMed [citation]
PMID:
19206169
PMCID:
PMC4028130
See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000197128.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The Asp638Glu variant in BRAF has been reported to have occurred de novo in two individuals with clinical features of Cardio-facio-cutaneous syndrome (Sarkozy 2 009, Kleefstra 2011). Another variant at this nucleotide position resulting in the same amino acid residue change has also been reported in two individuals wit h clinical features of Cardio-facio-cutaneous syndrome including one de novo occ urrence (Sarkozy 2009, Rauen 2006). This variant was not identified in large po pulation studies. Studies have shown that the Asp638Glu variant impacts protein function (Rodriguez-Viciana 2008). In summary, the Asp638Glu variant meets our c riteria to be classified as pathogenic (http://pcpgm.partners.org/LMM) based upo n its de novo occurrence in affected individuals, low allele frequency in the ge neral population, and supporting functional evidence.

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV005016614.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024