NM_001354689.3(RAF1):c.781C>A (p.Pro261Thr) AND Noonan syndrome

Clinical significance:Pathogenic (Last evaluated: Apr 15, 2011)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000037703.2

Allele description [Variation Report for NM_001354689.3(RAF1):c.781C>A (p.Pro261Thr)]

NM_001354689.3(RAF1):c.781C>A (p.Pro261Thr)

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.781C>A (p.Pro261Thr)
HGVS:
  • NC_000003.12:g.12604189G>T
  • NG_007467.1:g.64991C>A
  • NM_001354689.3:c.781C>AMANE SELECT
  • NM_001354690.3:c.781C>A
  • NM_001354691.3:c.538C>A
  • NM_001354692.3:c.538C>A
  • NM_001354693.3:c.682C>A
  • NM_001354694.3:c.538C>A
  • NM_001354695.3:c.439C>A
  • NM_002880.3:c.781C>A
  • NM_002880.4:c.781C>A
  • NP_001341618.1:p.Pro261Thr
  • NP_001341619.1:p.Pro261Thr
  • NP_001341620.1:p.Pro180Thr
  • NP_001341621.1:p.Pro180Thr
  • NP_001341622.1:p.Pro228Thr
  • NP_001341623.1:p.Pro180Thr
  • NP_001341624.1:p.Pro147Thr
  • NP_002871.1:p.Pro261Thr
  • NP_002871.1:p.Pro261Thr
  • LRG_413t1:c.781C>A
  • LRG_413t2:c.781C>A
  • LRG_413:g.64991C>A
  • LRG_413p1:p.Pro261Thr
  • LRG_413p2:p.Pro261Thr
  • NC_000003.11:g.12645688G>T
  • NC_000003.11:g.12645688G>T
  • NM_002880.2:c.781C>A
  • NR_148940.3:n.1112C>A
  • NR_148941.3:n.1112C>A
  • NR_148942.3:n.1112C>A
  • c.781C>A
Protein change:
P147T
Links:
dbSNP: rs121434594
NCBI 1000 Genomes Browser:
rs121434594
Molecular consequence:
  • NM_001354689.3:c.781C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354690.3:c.781C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354691.3:c.538C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354692.3:c.538C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354693.3:c.682C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354694.3:c.538C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354695.3:c.439C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.3:c.781C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002880.4:c.781C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148940.3:n.1112C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148941.3:n.1112C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148942.3:n.1112C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
2

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000061365Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Pathogenic
(Apr 15, 2011)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

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, Partners HealthCare Personalized Medicine, SCV000061365.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

The Pro261Thr variant has not been previously reported in the literature. This v ariant has been identified in one other proband with clinical features of Noonan syndrome tested by our laboratory and was found to have occurred de novo (LMM u npublished data). In addition, proline (Pro) at codon 261 is a highly conserved amino acid and other missense variants at this position (Pro261Ala, Pro261Leu, P ro261Arg, Pro261Ser) have previously been associated with Noonan syndrome (Razza que 2007, Pandit 2007). Therefore, the Pro261Thr variant is highly likely to be pathogenic. Individuals with pathogenic variants in exon 7 or 17 in RAF1 have a high incidence of hypertrophic cardiomyopathy (80-95%, Razzaque 2007).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: Oct 24, 2021

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