NM_001354689.3(RAF1):c.768G>T (p.Arg256Ser) AND not provided

Clinical significance:Pathogenic (Last evaluated: Mar 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001354689.3(RAF1):c.768G>T (p.Arg256Ser)]

NM_001354689.3(RAF1):c.768G>T (p.Arg256Ser)

RAF1:Raf-1 proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001354689.3(RAF1):c.768G>T (p.Arg256Ser)
Other names:
p.R256S:AGG>AGT; NM_002880.3(RAF1):c.768G>T
  • NC_000003.12:g.12604202C>A
  • NG_007467.1:g.64978G>T
  • NM_001354689.3:c.768G>TMANE SELECT
  • NM_001354690.2:c.768G>T
  • NM_001354691.2:c.525G>T
  • NM_001354692.2:c.525G>T
  • NM_001354693.2:c.669G>T
  • NM_001354694.2:c.525G>T
  • NM_001354695.2:c.426G>T
  • NM_002880.3:c.768G>T
  • NP_001341618.1:p.Arg256Ser
  • NP_001341619.1:p.Arg256Ser
  • NP_001341620.1:p.Arg175Ser
  • NP_001341621.1:p.Arg175Ser
  • NP_001341622.1:p.Arg223Ser
  • NP_001341623.1:p.Arg175Ser
  • NP_001341624.1:p.Arg142Ser
  • NP_002871.1:p.Arg256Ser
  • LRG_413t1:c.768G>T
  • LRG_413t2:c.768G>T
  • LRG_413:g.64978G>T
  • LRG_413p1:p.Arg256Ser
  • LRG_413p2:p.Arg256Ser
  • NC_000003.11:g.12645701C>A
  • NR_148940.2:n.1099G>T
  • NR_148941.2:n.1099G>T
  • NR_148942.2:n.1099G>T
  • P04049:p.Arg256Ser
  • c.768G>T
Protein change:
UniProtKB: P04049#VAR_037807; dbSNP: rs397516826
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001354689.3:c.768G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354690.2:c.768G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354691.2:c.525G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354692.2:c.525G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354693.2:c.669G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354694.2:c.525G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354695.2:c.426G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.3:c.768G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148940.2:n.1099G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148941.2:n.1099G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148942.2:n.1099G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000209014GeneDxcriteria provided, single submitter
(Mar 19, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000209014.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


Published functional studies demonstrate a damaging effect on protein localization and activity (Molzan et al., 2010); Identified in patients with Noonan syndrome and/or hypertrophic cardiomyopathy referred for genetic testing at GeneDx and in published literature (Pandit et al., 2007); Reported in ClinVar as pathogenic by another clinical laboratory and the ClinGen RASopathy Variant Curation Expert Panel (ClinVar Variant ID# 40599; SCV000616377.3, SCV000061363.5; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Located in the CR2 critical functional domain; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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