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NM_004333.6(BRAF):c.1914T>A (p.Asp638Glu) AND RASopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 16, 2021
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:
RCV001851863.5

Allele description [Variation Report for NM_004333.6(BRAF):c.1914T>A (p.Asp638Glu)]

NM_004333.6(BRAF):c.1914T>A (p.Asp638Glu)

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.1914T>A (p.Asp638Glu)
HGVS:
  • NC_000007.14:g.140749365A>T
  • NG_007873.3:g.180400T>A
  • NM_001354609.2:c.1914T>A
  • NM_001374244.1:c.2034T>A
  • NM_001374258.1:c.2034T>A
  • NM_001378467.1:c.1923T>A
  • NM_001378468.1:c.1914T>A
  • NM_001378469.1:c.1848T>A
  • NM_001378470.1:c.1812T>A
  • NM_001378471.1:c.1803T>A
  • NM_001378472.1:c.1758T>A
  • NM_001378473.1:c.1758T>A
  • NM_001378474.1:c.1914T>A
  • NM_001378475.1:c.1650T>A
  • NM_004333.6:c.1914T>AMANE 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>A
  • LRG_299:g.180400T>A
  • NC_000007.13:g.140449165A>T
  • NM_004333.4:c.1914T>A
  • P15056:p.Asp638Glu
Protein change:
D550E; ASP638GLU
Links:
UniProtKB: P15056#VAR_058630; OMIM: 164757.0021; dbSNP: rs180177042
NCBI 1000 Genomes Browser:
rs180177042
Molecular consequence:
  • NM_001354609.2:c.1914T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374244.1:c.2034T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374258.1:c.2034T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378467.1:c.1923T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378468.1:c.1914T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378469.1:c.1848T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378470.1:c.1812T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378471.1:c.1803T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378472.1:c.1758T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378473.1:c.1758T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378474.1:c.1914T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378475.1:c.1650T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004333.6:c.1914T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RASopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: C5555857

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002227991Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 16, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Distinguishing Costello versus cardio-facio-cutaneous syndrome: BRAF mutations in patients with a Costello phenotype.

Rauen KA.

Am J Med Genet A. 2006 Aug 1;140(15):1681-3. No abstract available.

PubMed [citation]
PMID:
16804887

Neurological complications of cardio-facio-cutaneous syndrome.

Yoon G, Rosenberg J, Blaser S, Rauen KA.

Dev Med Child Neurol. 2007 Dec;49(12):894-9.

PubMed [citation]
PMID:
18039235
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002227991.2

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

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRAF protein function. This missense change has been observed in individual(s) with BRAF-related conditions (PMID: 16804887, 18039235, 22495831, 19206169). ClinVar contains an entry for this variant (Variation ID: 13981). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 638 of the BRAF protein (p.Asp638Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024