ClinVar Genomic variation as it relates to human health
NM_004333.6(BRAF):c.770A>G (p.Gln257Arg)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004333.6(BRAF):c.770A>G (p.Gln257Arg)
Variation ID: 13973 Accession: VCV000013973.67
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q34 7: 140801502 (GRCh38) [ NCBI UCSC ] 7: 140501302 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jul 2, 2015 May 1, 2024 Apr 3, 2017 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004333.6:c.770A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004324.2:p.Gln257Arg missense NM_001374258.1:c.770A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001361187.1:p.Gln257Arg missense NM_001354609.2:c.770A>G NP_001341538.1:p.Gln257Arg missense NM_001374244.1:c.770A>G NP_001361173.1:p.Gln257Arg missense NM_001378467.1:c.779A>G NP_001365396.1:p.Gln260Arg missense NM_001378468.1:c.770A>G NP_001365397.1:p.Gln257Arg missense NM_001378469.1:c.770A>G NP_001365398.1:p.Gln257Arg missense NM_001378470.1:c.668A>G NP_001365399.1:p.Gln223Arg missense NM_001378471.1:c.770A>G NP_001365400.1:p.Gln257Arg missense NM_001378472.1:c.614A>G NP_001365401.1:p.Gln205Arg missense NM_001378473.1:c.614A>G NP_001365402.1:p.Gln205Arg missense NM_001378474.1:c.770A>G NP_001365403.1:p.Gln257Arg missense NM_001378475.1:c.506A>G NP_001365404.1:p.Gln169Arg missense NC_000007.14:g.140801502T>C NC_000007.13:g.140501302T>C NG_007873.3:g.128263A>G LRG_299:g.128263A>G LRG_299t1:c.770A>G P15056:p.Gln257Arg - Protein change
- Q257R, Q205R, Q223R, Q260R, Q169R
- Other names
- p.Q257R:CAG>CGG
- NM_004333.4(BRAF):c.770A>G
- Canonical SPDI
- NC_000007.14:140801501:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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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. |
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BRAF | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1230 | 1339 |
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. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Mar 26, 2024 | RCV000015007.42 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 19, 2023 | RCV000033289.25 | |
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Dec 19, 2022 | RCV000080904.42 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jun 16, 2023 | RCV001261967.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 2, 2019 | RCV001329219.9 | |
Pathogenic (5) |
reviewed by expert panel
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Apr 3, 2017 | RCV000208766.17 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2021 | RCV003224098.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 13, 2019 | RCV001027771.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 1, 2018 | RCV001813208.11 | |
Pathogenic (3) |
criteria provided, single submitter
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Jan 5, 2022 | RCV001813744.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 5, 2024 | RCV004018628.1 | |
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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. |
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Pathogenic
(Apr 03, 2017)
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reviewed by expert panel
Method: curation
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Cardio-facio-cutaneous syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen RASopathy Variant Curation Expert Panel
Accession: SCV000616360.4
First in ClinVar: Dec 19, 2017 Last updated: Dec 11, 2022 |
Comment:
The c.770A>G (p.Gln257Arg) variant in BRAF has been reported in the literature as a confirmed de novo occurrence in at least 2 patients with clinical … (more)
The c.770A>G (p.Gln257Arg) variant in BRAF has been reported in the literature as a confirmed de novo occurrence in at least 2 patients with clinical features of a RASopathy (PS2_VeryStrong; PMID:18042262, PMID:17551924, PMID:16474404). In vitro functional studies provide some evidence that the p.Q257R variant may impact protein function (PS3; PMID:18413255; PMID:19376813). This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org). The variant is located in the BRAF gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID:29493581). Furthermore, this variant is located in exon 6, which has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of BRAF (PM1; PMID:29493581). Computational prediction tools and conservation analysis suggest that the p.Q257R variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as pathogenic for cardio-facio-cutaneous syndrome in an autosomal dominant manner. Rasopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2, PP3, PM1, PM2, PS3, PS2_VeryStrong. (less)
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Pathogenic
(Jan 21, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiofaciocutaneous syndrome
Affected status: yes
Allele origin:
germline
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Courtagen Diagnostics Laboratory, Courtagen Life Sciences
Accession: SCV000236532.2
First in ClinVar: Jul 02, 2015 Last updated: Jul 02, 2015 |
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Pathogenic
(Jul 11, 2013)
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criteria provided, single submitter
Method: clinical testing
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Rasopathy
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Study: Adult_WES
Accession: SCV000245458.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
This variant has been previously reported as disease-causing and was found once in our laboratory as a de novo change in a 24-year-old female with … (more)
This variant has been previously reported as disease-causing and was found once in our laboratory as a de novo change in a 24-year-old female with intellectual disability, epilepsy, coarse facial features, short stature, microcephaly, and severe brain ischemia and hemiparesis following cardiac arrest at age 8y. (less)
Number of individuals with the variant: 1
Age: 20-29 years
Sex: female
Ethnicity/Population group: Hispanic Americans
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Pathogenic
(Jul 23, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown, yes
Allele origin:
unknown,
de novo
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Molecular Diagnostics Lab, Nemours Children's Health, Delaware
Accession: SCV000263061.1
First in ClinVar: Feb 20, 2016 Last updated: Feb 20, 2016 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Macrocephaly (present) , Prominent forehead (present) , Delay (present) , Hypertelorism (present) , Depressed nasal bridge (present) , Posteriorly rotated ears (present)
Age: 0-9 years
Sex: male
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Mental Retardation (present) , Pulmonic valve stenosis (present) , G-tube/reflux (present) , Texture aversions (present) , Sparse hair (present) , Normal chromosomes and PTPN11 testing … (more)
Mental Retardation (present) , Pulmonic valve stenosis (present) , G-tube/reflux (present) , Texture aversions (present) , Sparse hair (present) , Normal chromosomes and PTPN11 testing (present) (less)
Age: 0-9 years
Sex: female
Ethnicity/Population group: African American
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Dysmorphic features (present) , Hypertrophic cardiomyopathy (present) , Postnatal onset growth deficiency (present) , Developmental delay (present) , Downslanting palpebral fissures (present) , Depressed nasal … (more)
Dysmorphic features (present) , Hypertrophic cardiomyopathy (present) , Postnatal onset growth deficiency (present) , Developmental delay (present) , Downslanting palpebral fissures (present) , Depressed nasal bridge (present) , High arched palate (present) , Protruding nostrils (present) , Deep palmar and plantar creases (present) , Hyper-extensible fingers (present) , Sparse curly hair (present) , Central hypotonia (present) , Mental retardation (present) , Hypoplasia of corpus callosum (present) (less)
Age: 0-9 years
Sex: male
Geographic origin: Greece
Observation 4:
Number of individuals with the variant: 1
Age: 0-9 years
Sex: male
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Pathogenic
(Apr 26, 2013)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000112811.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 19, 2017 |
Sex: mixed
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Pathogenic
(Sep 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000927948.1
First in ClinVar: Jul 31, 2019 Last updated: Jul 31, 2019
Comment:
Patient analyzed with Noonan Syndrome Panel
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Cardiofaciocutaneous syndrome 1
Affected status: yes
Allele origin:
unknown
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Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn
Accession: SCV000999368.1
First in ClinVar: Dec 01, 2019 Last updated: Dec 01, 2019 |
Number of individuals with the variant: 1
Clinical Features:
High forehead (present) , Short stature (present) , Global developmental delay (present) , Depressed nasal bridge (present) , Flared nostrils (present) , Finger joint hypermobility … (more)
High forehead (present) , Short stature (present) , Global developmental delay (present) , Depressed nasal bridge (present) , Flared nostrils (present) , Finger joint hypermobility (present) , Deeply set eye (present) , Curly hair (present) , Alopecia (present) , Long fingers (present) , Long toe (present) , Muscular hypotonia (present) , Pectus carinatum (present) , Melanocytic nevus (present) , Short neck (present) , Sparse eyelashes (present) , Thick vermilion border (present) , Macrocephalus (present) , Sparse and thin eyebrow (present) , Prominent forehead (present) (less)
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiofaciocutaneous syndrome 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137523.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
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Pathogenic
(Aug 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiofaciocutaneous syndrome 1
LEOPARD syndrome 3 Noonan syndrome 7
Affected status: unknown
Allele origin:
germline
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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV001190375.1
First in ClinVar: Mar 26, 2020 Last updated: Mar 26, 2020 |
Comment:
BRAF NM_004333.4 exon 6 p.Gln257Arg (c.770A>G): This variant is considered to be a common disease variant and has been reported in the literature in several … (more)
BRAF NM_004333.4 exon 6 p.Gln257Arg (c.770A>G): This variant is considered to be a common disease variant and has been reported in the literature in several individuals with cardiofaciocutaneous syndrome (CFC) and other Noonan-spectrum disorders, including several de novo occurrences (Niihori 2006 PMID:16474404, Gripp 2007 PMID:17551924, Schulz 2008 PMID:18042262, Sarkozy 2009 PMID:19206169, Neumann 2009 PMID:18854871, Carcavilla 2013 PMID:24775816, Wong Ramsey 2014 PMID:24719372, Joyce 2016 PMID:26242988, Xu 2017 PMID:29084544). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic, including an entry from the ClinGen RASopathies Expert Panel (Variation ID:13973). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, both in vitro and in vivo functional studies support that this variant will impact the protein (Niihori 2006 PMID:16474404, Rodriguez-Viciana 2008 PMID:18403255, Anastasaki 2009 PMID:19376813, Inoue 2014 PMID:25035421). In summary, this variant is classified as pathogenic based on the data above. (less)
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Pathogenic
(Aug 22, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449679.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Aug 02, 2019)
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criteria provided, single submitter
Method: clinical testing
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LEOPARD syndrome 3
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001520594.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Apr 01, 2018)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome and Noonan-related syndrome
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002060974.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 1
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002061271.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.770A>G;p.(Gln257Arg) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 13973; OMIM: 164757.0013; PMID:18042262; 17551924; … (more)
The c.770A>G;p.(Gln257Arg) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 13973; OMIM: 164757.0013; PMID:18042262; 17551924; 16474404; 17703371; 24719372; 24775816) - PS4. Well-established in vitro or in vivo functional studies support a damaging effect on the gene or gene product (PMID:18413255; 19376813; 16474404) - PS3_moderate. The variant is located in a mutational hot spot and/or critical and well-established functional domain (C1_1; PMID: 29493581) - PM1. This variant is not present in population databases (rs180177035, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (ClinVar ID: 40351) - PM5. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID:18042262; 17551924) - PM6_strong. Missense variant in BRAF that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease - PP2. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(Jun 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000057194.18
First in ClinVar: Apr 04, 2013 Last updated: Mar 04, 2023 |
Comment:
Functional in vitro studies have demonstrated that the p.(Q257R) variant results in increased kinase activity and activation of downstream effectors (MEK and ERK) (Rodriguez-Viciana et … (more)
Functional in vitro studies have demonstrated that the p.(Q257R) variant results in increased kinase activity and activation of downstream effectors (MEK and ERK) (Rodriguez-Viciana et al., 2008), and in vivo studies have demostrated developmental defects and CFC-like features in animal models (Anastasaki et al., 2009; Moriya et al., 2015); Missense variants in this gene are often considered pathogenic (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17551924, 29778030, 29704308, 34573299, 17703371, 23312806, 16474404, 18042262, 19376813, 26472072, 26242988, 28809097, 27799561, 28650561, 29084544, 23340054, 30050098, 32005694, 32369273, 29907801, 33482860, 31130284, 27322245, 24719372, 24803665, 24775816, 33795686, 33040082, 33726816, 31785789, 33860439, 18413255, 29493581, 17603483, 15520807, 16439621, 15488754, 24957944) (less)
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Pathogenic
(Mar 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Melanoma, cutaneous malignant, susceptibility to, 1
LEOPARD syndrome 3 Cardiofaciocutaneous syndrome 1 Lung cancer Noonan syndrome 7 Colorectal cancer Lung cancer
Affected status: unknown
Allele origin:
germline
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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920481.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
BRAF NM_004333.4 exon 6 p.Gln257Arg (c.770A>G): This variant is considered to be a common disease variant and has been reported in the literature in several … (more)
BRAF NM_004333.4 exon 6 p.Gln257Arg (c.770A>G): This variant is considered to be a common disease variant and has been reported in the literature in several individuals with cardiofaciocutaneous syndrome (CFC) and other Noonan-spectrum disorders, including several de novo occurrences (Niihori 2006 PMID:16474404, Gripp 2007 PMID:17551924, Schulz 2008 PMID:18042262, Sarkozy 2009 PMID:19206169, Neumann 2009 PMID:18854871, Carcavilla 2013 PMID:24775816, Wong Ramsey 2014 PMID:24719372, Joyce 2016 PMID:26242988, Xu 2017 PMID:29084544). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic, including an entry from the ClinGen RASopathies Expert Panel (Variation ID:13973). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, both in vitro and in vivo functional studies support that this variant will impact the protein (Niihori 2006 PMID:16474404, Rodriguez-Viciana 2008 PMID:18403255, Anastasaki 2009 PMID:19376813, Inoue 2014 PMID:25035421). In summary, this variant is classified as pathogenic based on the data above. (less)
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Pathogenic
(Jun 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 7
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV003932627.1
First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023 |
Comment:
ACMG criteria used: PS3, PS4, PM2
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Pathogenic
(Dec 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602655.3
First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024 |
Comment:
The BRAF c.770A>G, p.Gln257Arg variant (rs180177035) has been reported in multiple patients diagnosed with LEOPARD syndrome, cardio-facial-cutaneous syndrome or other RASopathies (Niihori 2006, Rodriguez-Viciana 2006, … (more)
The BRAF c.770A>G, p.Gln257Arg variant (rs180177035) has been reported in multiple patients diagnosed with LEOPARD syndrome, cardio-facial-cutaneous syndrome or other RASopathies (Niihori 2006, Rodriguez-Viciana 2006, Gripp 2007, Narumi 2007, Nystrom 2008, Neumann 2009, Sarkozy 2009, Carcavilla 2013, Wong Ramsey 2014). The variant is located in the cysteine-rich domain of the BRAF conserved region 1 (Niihori 2006, Rodriguez-Viciana 2006), and several additional variants in neighboring codons have also been identified in cardio-facial-cutaneous syndrome (Kiel 2014). Functional analyses of the p.Gln257Arg variant protein indicates over-activation of phospho-MEK and phospho-ERK (Rodriguez-Viciana 2006, Rodriguez-Viciana 2008) and downstream transcriptional activity (Niihori 2006), consistent with the established disease mechanisms of BRAF-related disorders. This variant is reported in ClinVar (Variation ID: 13973) and is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamine at codon 257 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.838). Based on available information, this variant is considered to be pathogenic. References: Carcavilla A et al. LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. Rev Esp Cardiol (Engl Ed). 2013 May;66(5):350-6. PMID: 24775816. Gripp KW et al. Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome. Am J Med Genet A. 2007 Jul 1;143A(13):1472-80. PMID: 17551924.. Kiel C et al. Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations. Mol Syst Biol. 2014 May 6;10(5):727. PMID: 24803665. Narumi Y et al. Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome. Am J Med Genet A. 2007 Apr 15;143A(8):799-807. PMID: 17366577. Niihori T et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006 Mar;38(3):294-6. PMID: 16474404. Nystrom AM et al. Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders. J Med Genet. 2008 Aug;45(8):500-6. PMID: 18456719. Rodriguez-Viciana P et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science. 2006 Mar 3;311(5765):1287-90. PMID: 16439621. Rodriguez-Viciana P et al. Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome. Methods Enzymol. 2008;438:277-89. PMID: 18413255. Sarkozy A et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009 Apr;30(4):695-702. PMID: 19206169. (less)
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Pathogenic
(Sep 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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RASopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000218757.12
First in ClinVar: Mar 29, 2015 Last updated: Feb 28, 2024 |
Comment:
Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt BRAF function. … (more)
Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt BRAF function. ClinVar contains an entry for this variant (Variation ID: 13973). This missense change has been observed in individuals with Noonan spectrum disorders (PMID: 16474404, 17703371, 24719372, 24775816). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 257 of the BRAF protein (p.Gln257Arg). Experimental studies have shown that this missense change affects BRAF function (PMID: 16474404, 18413255). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. (less)
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cardiofaciocutaneous syndrome 1
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806738.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Aug 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001502611.17
First in ClinVar: Mar 14, 2021 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Apr 17, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardio-facio-cutaneous syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698346.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Comment:
Variant summary: The BRAF c.770A>G (p.Gln257Arg) variant involves the alteration of a conserved nucleotide, is predicted to be damaging by 3/4 in silico tools (SNPs&GO … (more)
Variant summary: The BRAF c.770A>G (p.Gln257Arg) variant involves the alteration of a conserved nucleotide, is predicted to be damaging by 3/4 in silico tools (SNPs&GO not captured due to low reliability index) and is located in acylglycerol/phorbol-ester binding domain of the protein (InterPro). This variant is absent from 118580 control chromosomes from ExAC dataset. The variant is widely accepted to be pathogenic in the literature with concordant clinical and functional data. It is frequently reported in patients with CFC including evidence of de novo occurrences. In vitro as well as in vivo functional evidences are consistent with pathogenic outcome. Several clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic. (less)
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Pathogenic
(Mar 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 7
Affected status: yes
Allele origin:
germline
|
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV003807319.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
ACMG classification criteria: PS2 strong, PS3 supporting, PS4 strong, PM1 moderated, PM2 moderated, PP1 supporting, PP3 supporting
Number of individuals with the variant: 1
Clinical Features:
Low-set ears (present) , Preauricular pit (present) , Micrognathia (present) , Large for gestational age (present) , Strabismus (present) , Pulmonic stenosis (present) , Depressed … (more)
Low-set ears (present) , Preauricular pit (present) , Micrognathia (present) , Large for gestational age (present) , Strabismus (present) , Pulmonic stenosis (present) , Depressed nasal bridge (present) , Short stature (present) , Global developmental delay (present) , Thick vermilion border (present) , Mild short stature (present) , Hypertelorism (present) , Bulbous nose (present) , Intellectual disability, mild (present) , Proportionate short stature (present) , Frontal bossing (present) , Long palpebral fissure (present) , Inguinal hernia (present) , High, narrow palate (present) , Cardiomyopathy (present) , Epicanthus (present) , Hypertrophic cardiomyopathy (present) (less)
Geographic origin: Brazil
Method: Paired-end whole-genome sequencing
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Pathogenic
(Jul 22, 2020)
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome 7
Affected status: yes
Allele origin:
de novo
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001439323.2
First in ClinVar: Oct 31, 2020 Last updated: Mar 26, 2023 |
Method: Exome sequencing
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Pathogenic
(Jan 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000742125.5
First in ClinVar: Apr 15, 2018 Last updated: May 01, 2024 |
Comment:
The p.Q257R pathogenic mutation (also known as c.770A>G), located in coding exon 6 of the BRAF gene, results from an A to G substitution at … (more)
The p.Q257R pathogenic mutation (also known as c.770A>G), located in coding exon 6 of the BRAF gene, results from an A to G substitution at nucleotide position 770. The glutamine at codon 257 is replaced by arginine, an amino acid with highly similar properties. This variant has been reported in multiple individuals with features consistent with BRAF-related RASopathy, including several de novo occurrences (Niihori T et al. Nat Genet, 2006 Mar;38:294-6; Gripp KW et al. Am J Med Genet A, 2007 Jul;143A:1472-80; Wong Ramsey KN et al. Am J Med Genet A, 2014 Aug;164A:2036-42; Joyce S et al. Eur J Hum Genet, 2016 May;24:690-6; Mucciolo M et al. Int J Mol Sci, 2016 Jun;17; Mellis R et al. BJOG, 2022 Jan;129:52-61). In an assay testing BRAF function, this variant showed a functionally abnormal result (Rodriguez-Viciana P et al. Methods Enzymol, 2008;438:277-89). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Mar 01, 2006)
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no assertion criteria provided
Method: literature only
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CARDIOFACIOCUTANEOUS SYNDROME 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000035263.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 22, 2016 |
Comment on evidence:
In 3 unrelated patients with cardiofaciocutaneous syndrome (CFC1; 115150), Niihori et al. (2006) found a heterozygous 770A-G transition in exon 6 of the BRAF gene, … (more)
In 3 unrelated patients with cardiofaciocutaneous syndrome (CFC1; 115150), Niihori et al. (2006) found a heterozygous 770A-G transition in exon 6 of the BRAF gene, predicting a gln257-to-arg (Q257R) amino acid change. (less)
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Pathogenic
(Jul 01, 2015)
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no assertion criteria provided
Method: clinical testing
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Cardio-facio-cutaneous syndrome
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000203920.4
First in ClinVar: Jan 31, 2015 Last updated: Dec 19, 2017 |
Comment:
The p.Gln257Arg variant in BRAF is an established pathogenic variant for Cardiof aciocutaneous syndrome (CFC) and is absent from large population studies. The p. Gln257Arg … (more)
The p.Gln257Arg variant in BRAF is an established pathogenic variant for Cardiof aciocutaneous syndrome (CFC) and is absent from large population studies. The p. Gln257Arg variant is one of the most commonly identified variants in BRAF and ha s been reported in >30 individuals with CFC syndrome (Rodriguez-Viciana 2008, Sa rkozy 2009, Neumann 2009, Abe 2012 Luk 2013, Wong Ramsey 2014, LMM unpublished d ata) and in 1 individual with LEOPARD syndrome (Carcavilla 2013). De novo occurr ences have been described for several individuals (Gripp 2007, Sarkozy 2009, Luk 2013, Neumann 2009, Niihori 2006). In addition, in vitro and in vivo functional studies support that this variant impacts protein function (Anastaski 2009, Ana stasaki 2012, Wen 2013, Inoue 2014). In summary, this variant meets our criteria to be classified as pathogenic for CFC syndrome in an autosomal dominant manner based upon de novo occurrence, absence from controls, and functional evidence. (less)
Number of individuals with the variant: 25
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Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Noonan syndrome 1
Affected status: yes
Allele origin:
unknown
|
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand
Accession: SCV003840166.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Number of individuals with the variant: 1
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
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Noonan syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Molecular Genetics, Centre for Human Genetics
Accession: SCV004190094.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Number of individuals with the variant: 2
Secondary finding: no
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Pathogenic
(Feb 08, 2022)
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no assertion criteria provided
Method: clinical testing
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Noonan syndrome 7
Affected status: yes
Allele origin:
de novo
|
Center for Molecular Medicine, Children’s Hospital of Fudan University
Accession: SCV002073930.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Sex: female
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not provided
(-)
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no classification provided
Method: phenotyping only
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Cardio-facio-cutaneous syndrome
Affected status: unknown, yes
Allele origin:
unknown
|
GenomeConnect - CFC International
Accession: SCV001156334.3
First in ClinVar: Feb 10, 2020 Last updated: Jan 08, 2022 |
Comment:
Variant identified in multiple registry participants. Variant interpreted as Pathogenic and reported, most recently on 04-27-2016 by lab or GTR ID GeneDx. Variant interpreted as … (more)
Variant identified in multiple registry participants. Variant interpreted as Pathogenic and reported, most recently on 04-27-2016 by lab or GTR ID GeneDx. Variant interpreted as Pathogenic and reported on 09-25-2012 by lab or GTR ID Central Manchester University Hospitals Regional Genetics Laboratory Services. Variant interpreted as Pathogenic and reported on 04-30-2009 by lab or GTR ID Prevention Genetics. 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. Phenotypic details are available under supporting information. (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Abnormality of eye movement (present) , Hypermetropia (present) , Myopia (present) , Ptosis (present) , Feeding difficulties (present) , Abnormal intestine morphology (present) , Joint … (more)
Abnormality of eye movement (present) , Hypermetropia (present) , Myopia (present) , Ptosis (present) , Feeding difficulties (present) , Abnormal intestine morphology (present) , Joint hypermobility (present) , Abnormal muscle physiology (present) , Cerebral palsy (present) , Cognitive impairment (present) , Seizure (present) , Delayed puberty (present) , Decreased response to growth hormone stimulation test (present) , Abnormality of the amniotic fluid (present) , Abnormal delivery (present) , Abnormal placenta morphology (present) , Premature birth (present) (less)
Indication for testing: Diagnostic
Age: 10-19 years
Sex: female
Testing laboratory: GeneDx
Date variant was reported to submitter: 2014-10-14
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Abnormality of eye movement (present) , Myopia (present) , Cognitive impairment (present) , Generalized hypotonia (present)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Testing laboratory: Central Manchester University Hospitals Regional Genetics Laboratory Services
Date variant was reported to submitter: 2012-09-25
Testing laboratory interpretation: Pathogenic
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Gastrointestinal dysmotility (present) , Feeding difficulties (present) , Abnormal intestine morphology (present) , Abnormal large intestine morphology (present) , Abnormality of the musculature of the … (more)
Gastrointestinal dysmotility (present) , Feeding difficulties (present) , Abnormal intestine morphology (present) , Abnormal large intestine morphology (present) , Abnormality of the musculature of the limbs (present) , Cognitive impairment (present) , Abnormality of coordination (present) , Hypertonia (present) , Seizure (present) , Decreased response to growth hormone stimulation test (present) , Abnormality of the amniotic fluid (present) , Anxiety (present) , Autistic behavior (present) , Compulsive behaviors (present) , Motor stereotypies (present) (less)
Age: 0-9 years
Sex: male
Testing laboratory: Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children
Date variant was reported to submitter: 2006-11-14
Testing laboratory interpretation: Pathogenic
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
Abnormality of vision (present) , Myopia (present) , Ptosis (present) , Hyperacusis (present) , Abnormal facial shape (present) , Abnormality of the neck (present) , … (more)
Abnormality of vision (present) , Myopia (present) , Ptosis (present) , Hyperacusis (present) , Abnormal facial shape (present) , Abnormality of the neck (present) , Abnormal cardiovascular system morphology (present) , Gastrointestinal dysmotility (present) , Feeding difficulties (present) , Abnormal stomach morphology (present) , Joint hypermobility (present) , Cognitive impairment (present) , Generalized hypotonia (present) , Seizure (present) , Delayed puberty (present) , Immunodeficiency (present) , Recurrent infections (present) (less)
Age: 10-19 years
Sex: female
Testing laboratory: GeneDx
Date variant was reported to submitter: 2009-08-26
Testing laboratory interpretation: Pathogenic
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
Abnormality of eye movement (present) , Hypermetropia (present) , Abnormality of vision (present) , Myopia (present) , Ptosis (present) , Abnormal facial shape (present) , … (more)
Abnormality of eye movement (present) , Hypermetropia (present) , Abnormality of vision (present) , Myopia (present) , Ptosis (present) , Abnormal facial shape (present) , Abnormal oral cavity morphology (present) , Abnormality of the neck (present) , Abnormality of the nose (present) , Gastrointestinal dysmotility (present) , Feeding difficulties (present) , Abnormal intestine morphology (present) , Abnormal large intestine morphology (present) , Abnormal stomach morphology (present) , Abnormality of the bladder (present) , Abnormal renal physiology (present) , Abnormal renal morphology (present) , Abnormality of the male genitalia (present) , Abnormality of the urethra (present) , Abnormality of the ureter (present) , Abnormal curvature of the vertebral column (present) , Joint hypermobility (present) , Abnormal skeletal muscle morphology (present) , Abnormal muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Abnormal morphology of the pelvis musculature (present) , Abnormality of the nervous system (present) , Cerebral palsy (present) , Cognitive impairment (present) , Generalized hypotonia (present) , Seizure (present) , Abnormality of the amniotic fluid (present) , Abnormal delivery (present) , Premature birth (present) , Autistic behavior (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Testing laboratory: PreventionGenetics,PreventionGenetics
Date variant was reported to submitter: 2009-04-30
Testing laboratory interpretation: Pathogenic
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
Abnormality of eye movement (present) , Hypermetropia (present) , Abnormality of vision (present) , Myopia (present) , Abnormal retinal morphology (present) , Abnormal facial shape … (more)
Abnormality of eye movement (present) , Hypermetropia (present) , Abnormality of vision (present) , Myopia (present) , Abnormal retinal morphology (present) , Abnormal facial shape (present) , Abnormal oral cavity morphology (present) , Abnormality of the neck (present) , Feeding difficulties (present) , Abnormality of the female genitalia (present) , Joint hypermobility (present) , Abnormality of the nervous system (present) , Cognitive impairment (present) , Generalized hypotonia (present) , Seizure (present) , Delayed puberty (present) , Decreased response to growth hormone stimulation test (present) , Premature birth (present) , Abnormality of the umbilical cord (present) (less)
Indication for testing: Diagnostic
Age: 20-29 years
Sex: female
Method: Sanger Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2016-04-27
Testing laboratory interpretation: Pathogenic
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not provided
(-)
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no classification provided
Method: literature only
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Cardio-facio-cutaneous syndrome
Affected status: yes
Allele origin:
germline
|
GeneReviews
Accession: SCV000264630.2
First in ClinVar: Mar 05, 2016 Last updated: Oct 01, 2022 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Cardiofaciocutaneous Syndrome. | Adam MP | - | 2023 | PMID: 20301365 |
Fetal exome sequencing for isolated increased nuchal translucency: should we be doing it? | Mellis R | BJOG : an international journal of obstetrics and gynaecology | 2022 | PMID: 34411415 |
Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement. | Le Duc D | European journal of medical genetics | 2020 | PMID: 30986545 |
Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia. | Schottmann G | Mitochondrion | 2017 | PMID: 28687512 |
Next Generation Sequencing Approach in a Prenatal Case of Cardio-Facio-Cutaneus Syndrome. | Mucciolo M | International journal of molecular sciences | 2016 | PMID: 27322245 |
Utility of whole exome sequencing for the early diagnosis of pediatric-onset cerebellar atrophy associated with developmental delay in an inbred population. | Megahed H | Orphanet journal of rare diseases | 2016 | PMID: 27146152 |
Molecular diagnostic experience of whole-exome sequencing in adult patients. | Posey JE | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26633545 |
The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. | Joyce S | European journal of human genetics : EJHG | 2016 | PMID: 26242988 |
New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. | Inoue S | Human molecular genetics | 2014 | PMID: 25035421 |
The perinatal presentation of cardiofaciocutaneous syndrome. | Wong Ramsey KN | American journal of medical genetics. Part A | 2014 | PMID: 24719372 |
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. | Eggens VR | Orphanet journal of rare diseases | 2014 | PMID: 24524299 |
LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. | Carcavilla A | Revista espanola de cardiologia (English ed.) | 2013 | PMID: 24775816 |
Single-molecule force measurement via optical tweezers reveals different kinetic features of two BRaf mutants responsible for cardio-facial-cutaneous (CFC) syndrome. | Wen C | Biomedical optics express | 2013 | PMID: 24409384 |
Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. | Zanni G | Neurogenetics | 2013 | PMID: 23975261 |
EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement. | Biancheri R | Journal of neurology | 2013 | PMID: 23564332 |
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 |
Continual low-level MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish. | Anastasaki C | Disease models & mechanisms | 2012 | PMID: 22301711 |
Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. | Lee BH | The Journal of pediatrics | 2011 | PMID: 21784453 |
Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors. | Anastasaki C | Human molecular genetics | 2009 | PMID: 19376813 |
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. | Sarkozy A | Human mutation | 2009 | PMID: 19206169 |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome. | Neumann TE | European journal of human genetics : EJHG | 2009 | PMID: 18854871 |
Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders. | Nyström AM | Journal of medical genetics | 2008 | PMID: 18456719 |
Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome. | Rodriguez-Viciana P | Methods in enzymology | 2008 | PMID: 18413255 |
Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome. | Schulz AL | Clinical genetics | 2008 | PMID: 18042262 |
Cardiofaciocutaneous (CFC) syndrome associated with muscular coenzyme Q10 deficiency. | Aeby A | Journal of inherited metabolic disease | 2007 | PMID: 17703371 |
Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome. | Gripp KW | American journal of medical genetics. Part A | 2007 | PMID: 17551924 |
Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome. | Narumi Y | American journal of medical genetics. Part A | 2007 | PMID: 17366577 |
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. | Niihori T | Nature genetics | 2006 | PMID: 16474404 |
Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. | Rodriguez-Viciana P | Science (New York, N.Y.) | 2006 | PMID: 16439621 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRAF | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/5f9417cc-43e4-41be-b920-ae6db397bdaa | - | - | - | - |
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Text-mined citations for rs180177035 ...
HelpRecord last updated May 01, 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.