ClinVar Genomic variation as it relates to human health
NM_002880.4(RAF1):c.786T>A (p.Asn262Lys)
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002880.4(RAF1):c.786T>A (p.Asn262Lys)
Variation ID: 44634 Accession: VCV000044634.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.2 3: 12604184 (GRCh38) [ NCBI UCSC ] 3: 12645683 (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 May 27, 2015 Sep 16, 2024 Apr 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002880.4:c.786T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002871.1:p.Asn262Lys missense NM_001354689.3:c.786T>A NP_001341618.1:p.Asn262Lys missense NM_001354690.3:c.786T>A NP_001341619.1:p.Asn262Lys missense NM_001354691.3:c.543T>A NP_001341620.1:p.Asn181Lys missense NM_001354692.3:c.543T>A NP_001341621.1:p.Asn181Lys missense NM_001354693.3:c.687T>A NP_001341622.1:p.Asn229Lys missense NM_001354694.3:c.543T>A NP_001341623.1:p.Asn181Lys missense NM_001354695.3:c.444T>A NP_001341624.1:p.Asn148Lys missense NR_148940.3:n.1117T>A non-coding transcript variant NR_148941.3:n.1117T>A non-coding transcript variant NR_148942.3:n.1117T>A non-coding transcript variant NC_000003.12:g.12604184A>T NC_000003.11:g.12645683A>T NG_007467.1:g.64996T>A LRG_413:g.64996T>A LRG_413t1:c.786T>A LRG_413p1:p.Asn262Lys LRG_413t2:c.786T>A LRG_413p2:p.Asn262Lys - Protein change
- N262K, N148K, N229K, N181K
- Other names
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- Canonical SPDI
- NC_000003.12:12604183:A:T
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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
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The frequency of the allele represented by this VCV record.
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- 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 | ||
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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
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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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RAF1 | No evidence available | No evidence available |
GRCh38 GRCh37 |
1235 | 1290 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (1) |
criteria provided, single submitter
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Sep 24, 2014 | RCV000037707.6 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Apr 17, 2023 | RCV000388842.8 |
Submissions - Germline
Classification
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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
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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
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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
(Sep 24, 2014)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Noonan syndrome
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061369.6
First in ClinVar: May 03, 2013 Last updated: May 27, 2015 |
Comment:
The Asn262Lys variant has been reported in two individuals with clinical feature s of a RASopathy and was identified to occur de novo in both … (more)
The Asn262Lys variant has been reported in two individuals with clinical feature s of a RASopathy and was identified to occur de novo in both individuals (Kobaya shi 2010, LMM unpublished). It was absent from large population studies. Computa tional prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determin e pathogenicity. In vitro functional studies provide some evidence that the Asn2 62Lys variant may impact protein function (Chan 2002, Kobayashi 2010). However, these types of assays may not accurately represent biological function. Individu als with pathogenic variants in exon 7 or 17 in RAF1 have a high incidence of hy pertrophic cardiomyopathy (80-95%, Chan 2002). In summary, this variant meets ou r criteria to be classified as pathogenic (http://pcpgmwww.partners.org/personal izedmedicince/LMM). (less)
Number of individuals with the variant: 1
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Pathogenic
(May 13, 2019)
C
Contributing to aggregate classification
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001714080.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PM1, PM2, PM5, PM6_Strong, PS3_Moderate
Number of individuals with the variant: 1
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Likely pathogenic
(Jul 13, 2022)
C
Contributing to aggregate classification
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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 Laboratory, Skane University Hospital Lund
Accession: SCV005198034.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Apr 17, 2023)
C
Contributing to aggregate classification
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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: SCV000329734.8
First in ClinVar: Dec 06, 2016 Last updated: Sep 16, 2024 |
Comment:
Published functional studies demonstrate a damaging effect with enhanced ELK transactivation and activated downstream ERK phosphorylation (PMID: 20052757); In silico analysis supports that this missense … (more)
Published functional studies demonstrate a damaging effect with enhanced ELK transactivation and activated downstream ERK phosphorylation (PMID: 20052757); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30732632, 32870709, 29493581, 20052757, 24957944, 9689060, 15520807, 17603483, 17603482, 19020799) (less)
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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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Clinical and mutation profile of pediatric patients with RASopathy-associated hypertrophic cardiomyopathy: results from a Chinese cohort. | Chen H | Orphanet journal of rare diseases | 2019 | PMID: 30732632 |
Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation. | Kobayashi T | Human mutation | 2010 | PMID: 20052757 |
Mutations in conserved regions 1, 2, and 3 of Raf-1 that activate transforming activity. | Chan EY | Molecular carcinogenesis | 2002 | PMID: 11933072 |
Text-mined citations for rs397516829 ...
HelpRecord last updated Mar 22, 2025
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.