NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly) AND Noonan syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 11, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000037675.7

Allele description [Variation Report for NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly)]

NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly)

Gene:

RAF1:Raf-1 proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.2

Genomic location:

Preferred name:

NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly)

HGVS:

NC_000003.12:g.12585760T>C
NG_007467.1:g.83420A>G
NM_001354689.3:c.1517A>G
NM_001354690.3:c.1457A>G
NM_001354691.3:c.1214A>G
NM_001354692.3:c.1214A>G
NM_001354693.3:c.1358A>G
NM_001354694.3:c.1274A>G
NM_001354695.3:c.1115A>G
NM_002880.4:c.1457A>GMANE SELECT
NP_001341618.1:p.Asp506Gly
NP_001341619.1:p.Asp486Gly
NP_001341620.1:p.Asp405Gly
NP_001341621.1:p.Asp405Gly
NP_001341622.1:p.Asp453Gly
NP_001341623.1:p.Asp425Gly
NP_001341624.1:p.Asp372Gly
NP_002871.1:p.Asp486Gly
NP_002871.1:p.Asp486Gly
LRG_413t1:c.1457A>G
LRG_413t2:c.1517A>G
LRG_413:g.83420A>G
LRG_413p1:p.Asp486Gly
LRG_413p2:p.Asp506Gly
NC_000003.11:g.12627259T>C
NM_002880.3:c.1457A>G
NR_148940.3:n.1901A>G
NR_148941.3:n.1847A>G
NR_148942.3:n.1786A>G
P04049:p.Asp486Gly
c.1457A>G

Protein change:

D372G

Links:

UniProtKB: P04049#VAR_037816; dbSNP: rs397516815

NCBI 1000 Genomes Browser:

rs397516815

Molecular consequence:

NM_001354689.3:c.1517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.1457A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.1214A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.1214A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.1358A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.1274A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.1115A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.1457A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.1901A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.1847A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.1786A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061337	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Feb 11, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17603483, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061337

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Feb 11, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.

Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, López Siguero JP, Tenconi R, Selicorni A, Rossi C, Mazzanti L, Torrente I, et al.

Nat Genet. 2007 Aug;39(8):1007-12. Epub 2007 Jul 1.

PubMed [citation]

PMID:: 17603483

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061337.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

proposed classification - variant undergoing re-assessment, contact laboratory

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Apr 13, 2025

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