Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; The majority of missense variants in this gene are considered pathogenic [(HGMD]; This variant is associated with the following publications: (PMID: 27171548, 30141192, 23093928, 25525159, 19206169, 18413255, 21063443, 30556322, 32369273, 33040082, 31069529, 34643321)
ClinVar Genomic variation as it relates to human health
NM_004333.6(BRAF):c.1914T>G (p.Asp638Glu)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(13)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
13
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004333.6(BRAF):c.1914T>G (p.Asp638Glu)
Variation ID: 162797 Accession: VCV000162797.49
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q34 7: 140749365 (GRCh38) [ NCBI UCSC ] 7: 140449165 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 2, 2015 Nov 17, 2024 Mar 14, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004333.6:c.1914T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004324.2:p.Asp638Glu missense NM_001374258.1:c.2034T>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001361187.1:p.Asp678Glu missense NM_001354609.2:c.1914T>G NP_001341538.1:p.Asp638Glu missense NM_001374244.1:c.2034T>G NP_001361173.1:p.Asp678Glu missense NM_001378467.1:c.1923T>G NP_001365396.1:p.Asp641Glu missense NM_001378468.1:c.1914T>G NP_001365397.1:p.Asp638Glu missense NM_001378469.1:c.1848T>G NP_001365398.1:p.Asp616Glu missense NM_001378470.1:c.1812T>G NP_001365399.1:p.Asp604Glu missense NM_001378471.1:c.1803T>G NP_001365400.1:p.Asp601Glu missense NM_001378472.1:c.1758T>G NP_001365401.1:p.Asp586Glu missense NM_001378473.1:c.1758T>G NP_001365402.1:p.Asp586Glu missense NM_001378474.1:c.1914T>G NP_001365403.1:p.Asp638Glu missense NM_001378475.1:c.1650T>G NP_001365404.1:p.Asp550Glu missense NC_000007.14:g.140749365A>C NC_000007.13:g.140449165A>C NG_007873.3:g.180400T>G LRG_299:g.180400T>G LRG_299t1:c.1914T>G P15056:p.Asp638Glu - Protein change
- D638E, D601E, D604E, D641E, D586E, D616E, D678E, D550E
- Other names
-
p.D638E:GAT>GAG
- Canonical SPDI
- NC_000007.14:140749364:A:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRAF | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1254 | 1368 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 14, 2024 | RCV000150199.7 | |
| Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 28, 2022 | RCV000157831.32 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 5, 2017 | RCV000624589.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 28, 2022 | RCV000689333.8 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Aug 16, 2018 | RCV000767527.3 | |
| not provided (1) |
no classification provided
|
- | RCV000999624.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Sep 7, 2023 | RCV004783752.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Aug 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiofaciocutaneous syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Genomic Medicine Lab, University of California San Francisco
Study: CSER
Accession: SCV001167600.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Sex: male
Secondary finding: no
|
|
|
Pathogenic
(Dec 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000207761.13
First in ClinVar: Feb 24, 2015 Last updated: Jan 07, 2023 |
Comment:
Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; The majority of … (more)
Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; The majority of missense variants in this gene are considered pathogenic [(HGMD]; This variant is associated with the following publications: (PMID: 27171548, 30141192, 23093928, 25525159, 19206169, 18413255, 21063443, 30556322, 32369273, 33040082, 31069529, 34643321) (less)
|
|
|
Pathogenic
(Nov 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247573.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Sep 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Noonan syndrome 7
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center
Accession: SCV005397313.1
First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024 |
Comment:
This sequence variant is a single nucleotide substitution (T>G) at position 1914 of the coding sequence of the BRAF gene that results in a aspartic … (more)
This sequence variant is a single nucleotide substitution (T>G) at position 1914 of the coding sequence of the BRAF gene that results in a aspartic acid to glutamic acid amino acid change at residue 638 of the B-Raf proto-oncogene, serine/threonine kise protein. The 638 residue falls in the kise domain (PMID: 18413255) which plays a critical role in BRAF function. This is a previously reported variant (ClinVar 162797) that has been observed in individuals affected by Costello syndrome (PMID: 16804887, 31069529) and cardiofaciocutaneous syndrome (PMID: 19206169, 37138575, 20859831, 21063443, 33040082, 27391121, 29095811, 22495831, 18039235, 37510243, 27940666, 31217210, 35524774, 34573299, 32369273), several of which were confirmed de novo (PMID: 19206169, 37138575, 20859831, 21063443). This variant is absent from the gnomAD population database (0/~250,000 alleles). Multiple bioinformatic tools predict that this Asp to Glu amino acid change would be damaging, and the Asp638 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functiol consequence of this variant demonstrate impaired kise activity (PMID: 18413255). Based upon the evidence, we consider this variant to be pathogenic. ACMG Criteria: PM2, PP2, PP3, PS1, PS3 (less)
|
|
|
Pathogenic
(Aug 27, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
Cardio-facio-cutaneous syndrome
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000197128.4
First in ClinVar: Feb 02, 2015 Last updated: Feb 02, 2015 |
Comment:
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, … (more)
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. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jan 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000742118.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Infantile spasms (present) , Seizures (present) , Severe global developmental delay (present) , Intellectual disability, profound (present) , Hypertonia (present) , Microcephaly (present) , Cortical … (more)
Infantile spasms (present) , Seizures (present) , Severe global developmental delay (present) , Intellectual disability, profound (present) , Hypertonia (present) , Microcephaly (present) , Cortical visual impairment (present) , Exotropia (present) , Cerebral atrophy (present) , Infantile muscular hypotonia (present) , Hyperreflexia (present) , Functional abnormality of the gastrointestinal tract (present) , Failure to thrive (present) , Hypoplasia of the corpus callosum (present) , Abnormality of muscle fibers (present) (less)
Sex: male
Ethnicity/Population group: Hispanic
|
|
|
Pathogenic
(Aug 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
RASopathy
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000816979.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRAF function (PMID: 18413255). Advanced modeling … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRAF function (PMID: 18413255). 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. ClinVar contains an entry for this variant (Variation ID: 162797). This missense change has been observed in individual(s) with cardio-facio-cutaneous syndrome (CFC) and Costello syndrome (PMID: 16804887, 18039235, 22495831). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 638 of the BRAF protein (p.Asp638Glu). (less)
|
|
|
Pathogenic
(Mar 14, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiofaciocutaneous syndrome
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV005016614.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932077.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001959358.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Pathogenic
(Sep 21, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Cardiofaciocutaneous syndrome 1
Affected status: yes
Allele origin:
de novo
|
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals
Accession: SCV000898145.1
First in ClinVar: Apr 21, 2019 Last updated: Apr 21, 2019 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809483.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Noonan syndrome 1
Affected status: yes
Allele origin:
unknown
|
GenomeConnect - CFC International
Accession: SCV001156331.1
First in ClinVar: Feb 07, 2020 Last updated: Feb 07, 2020 |
Comment:
Variant interpreted as Pathogenic and reported on 10-13-2014 by Lab or GTR ID 26957. GenomeConnect-CFC International assertions are reported exactly as they appear on the … (more)
Variant interpreted as Pathogenic and reported on 10-13-2014 by Lab or GTR ID 26957. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of eye movement (present) , Abnormality of globe size (present) , Feeding difficulties (present) , Abnormality of the stomach (present) , Abnormality of the … (more)
Abnormality of eye movement (present) , Abnormality of globe size (present) , Feeding difficulties (present) , Abnormality of the stomach (present) , Abnormality of the musculature of the limbs (present) , Abnormality of the musculature of the pelvis (present) , Epidermal thickening (present) , Generalized hypotonia (present) , Seizures (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Testing laboratory: GeneDx
Date variant was reported to submitter: 2014-10-13
Testing laboratory interpretation: Pathogenic
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Comment:
Comment:
This sequence variant is a single nucleotide substitution (T>G) at position 1914 of the coding sequence of the BRAF gene that results in a aspartic acid to glutamic acid amino acid change at residue 638 of the B-Raf proto-oncogene, serine/threonine kise protein. The 638 residue falls in the kise domain (PMID: 18413255) which plays a critical role in BRAF function. This is a previously reported variant (ClinVar 162797) that has been observed in individuals affected by Costello syndrome (PMID: 16804887, 31069529) and cardiofaciocutaneous syndrome (PMID: 19206169, 37138575, 20859831, 21063443, 33040082, 27391121, 29095811, 22495831, 18039235, 37510243, 27940666, 31217210, 35524774, 34573299, 32369273), several of which were confirmed de novo (PMID: 19206169, 37138575, 20859831, 21063443). This variant is absent from the gnomAD population database (0/~250,000 alleles). Multiple bioinformatic tools predict that this Asp to Glu amino acid change would be damaging, and the Asp638 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functiol consequence of this variant demonstrate impaired kise activity (PMID: 18413255). Based upon the evidence, we consider this variant to be pathogenic. ACMG Criteria: PM2, PP2, PP3, PS1, PS3
Comment:
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.
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRAF function (PMID: 18413255). 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. ClinVar contains an entry for this variant (Variation ID: 162797). This missense change has been observed in individual(s) with cardio-facio-cutaneous syndrome (CFC) and Costello syndrome (PMID: 16804887, 18039235, 22495831). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 638 of the BRAF protein (p.Asp638Glu).
Comment:
Variant interpreted as Pathogenic and reported on 10-13-2014 by Lab or GTR ID 26957. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.
Germline Functional Evidence
| 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. |
Comment:
Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; The majority of missense variants in this gene are considered pathogenic [(HGMD]; This variant is associated with the following publications: (PMID: 27171548, 30141192, 23093928, 25525159, 19206169, 18413255, 21063443, 30556322, 32369273, 33040082, 31069529, 34643321)
Comment:
This sequence variant is a single nucleotide substitution (T>G) at position 1914 of the coding sequence of the BRAF gene that results in a aspartic acid to glutamic acid amino acid change at residue 638 of the B-Raf proto-oncogene, serine/threonine kise protein. The 638 residue falls in the kise domain (PMID: 18413255) which plays a critical role in BRAF function. This is a previously reported variant (ClinVar 162797) that has been observed in individuals affected by Costello syndrome (PMID: 16804887, 31069529) and cardiofaciocutaneous syndrome (PMID: 19206169, 37138575, 20859831, 21063443, 33040082, 27391121, 29095811, 22495831, 18039235, 37510243, 27940666, 31217210, 35524774, 34573299, 32369273), several of which were confirmed de novo (PMID: 19206169, 37138575, 20859831, 21063443). This variant is absent from the gnomAD population database (0/~250,000 alleles). Multiple bioinformatic tools predict that this Asp to Glu amino acid change would be damaging, and the Asp638 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functiol consequence of this variant demonstrate impaired kise activity (PMID: 18413255). Based upon the evidence, we consider this variant to be pathogenic. ACMG Criteria: PM2, PP2, PP3, PS1, PS3
Comment:
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.
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRAF function (PMID: 18413255). 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. ClinVar contains an entry for this variant (Variation ID: 162797). This missense change has been observed in individual(s) with cardio-facio-cutaneous syndrome (CFC) and Costello syndrome (PMID: 16804887, 18039235, 22495831). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 638 of the BRAF protein (p.Asp638Glu).
Comment:
Variant interpreted as Pathogenic and reported on 10-13-2014 by Lab or GTR ID 26957. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The "FEEDS (FEeding Eating Deglutition Skills)" over Time Study in Cardiofaciocutaneous Syndrome. | Onesimo R | Genes | 2023 | PMID: 37510243 |
| Case report: Gastroenterological management in a case of cardio-facio-cutaneous syndrome. | Ciacchini B | Frontiers in pediatrics | 2023 | PMID: 37138575 |
| Neurologic and neurodevelopmental complications in cardiofaciocutaneous syndrome are associated with genotype: A multinational cohort study. | Pierpont EI | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 35524774 |
| Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations. | Battaglia DI | Genes | 2021 | PMID: 34573299 |
| Clinical and molecular spectra of BRAF-associated RASopathy. | Lee Y | Journal of human genetics | 2021 | PMID: 33040082 |
| Consecutive medical exome analysis at a tertiary center: Diagnostic and health-economic outcomes. | Kosaki R | American journal of medical genetics. Part A | 2020 | PMID: 32369273 |
| Endocrine abnormalities in cardiofaciocutaneous syndrome: a case of precocious puberty, hyperprolactinemia and diabetes insipidus. | Lenet S | BMJ case reports | 2019 | PMID: 31217210 |
| Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients. | Ganapathy A | Journal of neurology | 2019 | PMID: 31069529 |
| Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of prospective annual reanalysis. | Nambot S | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29095811 |
| RASopathies Are Associated With Delayed Puberty; Are They Associated With Precocious Puberty Too? | van der Kaay DC | Pediatrics | 2016 | PMID: 27940666 |
| Whole exome sequencing diagnosis of inborn errors of metabolism and other disorders in United Arab Emirates. | Al-Shamsi A | Orphanet journal of rare diseases | 2016 | PMID: 27391121 |
| Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan: findings from a nationwide epidemiological survey. | Abe Y | American journal of medical genetics. Part A | 2012 | PMID: 22495831 |
| Mitochondrial dysfunction and organic aciduria in five patients carrying mutations in the Ras-MAPK pathway. | Kleefstra T | European journal of human genetics : EJHG | 2011 | PMID: 21063443 |
| Cardio-facio-cutaneous syndrome: phenotypic variability and differential diagnosis in 3 cases with de novo BRAF mutations. | Demir E | Neuropediatrics | 2010 | PMID: 20859831 |
| Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. | Sarkozy A | Human mutation | 2009 | PMID: 19206169 |
| Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome. | Rodriguez-Viciana P | Methods in enzymology | 2008 | PMID: 18413255 |
| Neurological complications of cardio-facio-cutaneous syndrome. | Yoon G | Developmental medicine and child neurology | 2007 | PMID: 18039235 |
| Distinguishing Costello versus cardio-facio-cutaneous syndrome: BRAF mutations in patients with a Costello phenotype. | Rauen KA | American journal of medical genetics. Part A | 2006 | PMID: 16804887 |
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Text-mined citations for rs180177042 ...
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the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
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Record last updated Nov 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.