NM_000267.3(NF1):c.4168C>T (p.Leu1390Phe) AND Neurofibromatosis-Noonan syndrome

Clinical significance:Pathogenic (Last evaluated: Dec 1, 2009)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000023983.5

Allele description [Variation Report for NM_000267.3(NF1):c.4168C>T (p.Leu1390Phe)]

NM_000267.3(NF1):c.4168C>T (p.Leu1390Phe)

Gene:
NF1:neurofibromin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q11.2
Genomic location:
Preferred name:
NM_000267.3(NF1):c.4168C>T (p.Leu1390Phe)
HGVS:
  • NC_000017.11:g.31258401C>T
  • NG_009018.1:g.168425C>T
  • NM_000267.3:c.4168C>T
  • NM_001042492.2:c.4231C>T
  • NP_000258.1:p.Leu1390Phe
  • NP_001035957.1:p.Leu1411Phe
  • LRG_214t1:c.4168C>T
  • LRG_214t2:c.4231C>T
  • LRG_214:g.168425C>T
  • LRG_214p1:p.Leu1390Phe
  • LRG_214p2:p.Leu1411Phe
  • NC_000017.10:g.29585419C>T
Protein change:
L1390F; LEU1390PHE
Links:
UniProtKB/Swiss-Prot: VAR_065236; OMIM: 613113.0045; dbSNP: rs199474789
NCBI 1000 Genomes Browser:
rs199474789
Molecular consequence:
  • NM_000267.3:c.4168C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042492.2:c.4231C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neurofibromatosis-Noonan syndrome (NFNS)
Synonyms:
Neurofibromatosis with Noonan phenotype
Identifiers:
MONDO: MONDO:0011035; MedGen: C2931482; Orphanet: 638; OMIM: 601321

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000045274OMIMno assertion criteria providedPathogenic
(Dec 1, 2009)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1.

Nyström AM, Ekvall S, Allanson J, Edeby C, Elinder M, Holmström G, Bondeson ML, Annerén G.

Clin Genet. 2009 Dec;76(6):524-34. doi: 10.1111/j.1399-0004.2009.01233.x. Epub 2009 Oct 21.

PubMed [citation]
PMID:
19845691

Noonan syndrome with café-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus.

Ahlbom BE, Dahl N, Zetterqvist P, Annerén G.

Clin Genet. 1995 Aug;48(2):85-9.

PubMed [citation]
PMID:
7586657

Details of each submission

From OMIM, SCV000045274.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In affected members of a 5-generation family with neurofibromatosis-Noonan syndrome (NFNS; 601321), Nystrom et al. (2009) identified a heterozygous 4168C-T transition in exon 24 of the NF1 gene, resulting in a leu1390-to-phe (L1390F) substitution in the highly conserved GAP-related domain. The family was originally reported by Ahlbom et al. (1995) as having Noonan syndrome based on dysmorphic facial features, short stature, pulmonary stenosis, and short neck. Upon reevaluation, Nystrom et al. (2009) found that several family members had cafe-au-lait spots, axillary freckling, Lisch nodules, and multiple nevi, consistent with NF1, but that all family members lacked dermal and superficial plexiform neurofibromas. The authors concluded that the clinical diagnosis was consistent with NFNS. Nystrom et al. (2009) postulated that the L1390F mutation resulted in impaired GTPase activity.

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

Last Updated: May 10, 2021

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