NM_001354689.3(RAF1):c.782C>G (p.Pro261Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jul 14, 2015)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000159077.2

Allele description [Variation Report for NM_001354689.3(RAF1):c.782C>G (p.Pro261Arg)]

NM_001354689.3(RAF1):c.782C>G (p.Pro261Arg)

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_001354689.3(RAF1):c.782C>G (p.Pro261Arg)
Other names:
p.P261R:CCT>CGT
HGVS:
  • NC_000003.12:g.12604188G>C
  • NG_007467.1:g.64992C>G
  • NM_001354689.3:c.782C>GMANE SELECT
  • NM_001354690.2:c.782C>G
  • NM_001354691.2:c.539C>G
  • NM_001354692.2:c.539C>G
  • NM_001354693.2:c.683C>G
  • NM_001354694.2:c.539C>G
  • NM_001354695.2:c.440C>G
  • NM_002880.3:c.782C>G
  • NP_001341618.1:p.Pro261Arg
  • NP_001341619.1:p.Pro261Arg
  • NP_001341620.1:p.Pro180Arg
  • NP_001341621.1:p.Pro180Arg
  • NP_001341622.1:p.Pro228Arg
  • NP_001341623.1:p.Pro180Arg
  • NP_001341624.1:p.Pro147Arg
  • NP_002871.1:p.Pro261Arg
  • LRG_413t1:c.782C>G
  • LRG_413t2:c.782C>G
  • LRG_413:g.64992C>G
  • LRG_413p1:p.Pro261Arg
  • LRG_413p2:p.Pro261Arg
  • NC_000003.11:g.12645687G>C
  • NR_148940.2:n.1113C>G
  • NR_148941.2:n.1113C>G
  • NR_148942.2:n.1113C>G
  • c.782C>G
Protein change:
P147R
Links:
dbSNP: rs397516828
NCBI 1000 Genomes Browser:
rs397516828
Molecular consequence:
  • NM_001354689.3:c.782C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354690.2:c.782C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354691.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354692.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354693.2:c.683C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354694.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354695.2:c.440C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.3:c.782C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148940.2:n.1113C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148941.2:n.1113C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148942.2:n.1113C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000209020GeneDxcriteria provided, single submitter
Pathogenic
(Jan 10, 2014)
germlineclinical testing

Citation Link,

SCV000333074EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Jul 14, 2015)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

Germline gain-of-function mutations in RAF1 cause Noonan syndrome.

Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M, Momma K, Katayama H, Nakagawa M, Fujiwara Y, Matsushima M, Mizuno K, Tokuyama M, Hirota H, Muneuchi J, Higashinakagawa T, Matsuoka R.

Nat Genet. 2007 Aug;39(8):1013-7. Epub 2007 Jul 1.

PubMed [citation]
PMID:
17603482

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
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000209020.10

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

Description

The P261R missense mutation was identified in the RAF1 gene. It has not been published as a pathogenic variant or benign polymorphism, to our knowledge. However, this variant has been observed previously in multiple unrelated patients referred for Noonan syndrome testing. P261R is a non-conservative missense mutation that occurs in a highly conserved portion of the RAF1 gene, at an amino acid residue where many other gain-of-function variants (P261A, P261S and P261L) have also been reported in Noonan syndrome (Pandit et al., 2007 and Razzaque et al., 2007). Therefore, P261R is considered to be a pathogenic variant that is consistent with a diagnosis of an autosomal dominant RAF1-related disorder.

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

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000333074.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Jul 7, 2021

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