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NM_005188.4(CBL):c.1186T>C (p.Cys396Arg) AND Noonan syndrome-like disorder with juvenile myelomonocytic leukemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 1, 2010
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000022699.22

Allele description [Variation Report for NM_005188.4(CBL):c.1186T>C (p.Cys396Arg)]

NM_005188.4(CBL):c.1186T>C (p.Cys396Arg)

Gene:
CBL:Cbl proto-oncogene [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.3
Genomic location:
Preferred name:
NM_005188.4(CBL):c.1186T>C (p.Cys396Arg)
Other names:
p.C396R:TGT>CGT
HGVS:
  • NC_000011.10:g.119278256T>C
  • NG_016808.1:g.76977T>C
  • NM_005188.4:c.1186T>CMANE SELECT
  • NP_005179.2:p.Cys396Arg
  • LRG_608:g.76977T>C
  • NC_000011.9:g.119148966T>C
  • NM_005188.2:c.1186T>C
Protein change:
C396R; CYS396ARG
Links:
OMIM: 165360.0008; dbSNP: rs387906665
NCBI 1000 Genomes Browser:
rs387906665
Molecular consequence:
  • NM_005188.4:c.1186T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
Identifiers:
MedGen: C4016301

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000043988OMIM
no assertion criteria provided
Pathogenic
(Sep 1, 2010) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia.

Niemeyer CM, Kang MW, Shin DH, Furlan I, Erlacher M, Bunin NJ, Bunda S, Finklestein JZ, Gorr TA, Mehta P, Schmid I, Kropshofer G, Corbacioglu S, Lang PJ, Klein C, Schlegel PG, Heinzmann A, Schneider M, Starý J, van den Heuvel-Eibrink MM, Hasle H, Locatelli F, et al.

Nat Genet. 2010 Sep;42(9):794-800. doi: 10.1038/ng.641. Epub 2010 Aug 8.

PubMed [citation]
PMID:
20694012
PMCID:
PMC4297285

Details of each submission

From OMIM, SCV000043988.2

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

Description

In a male infant with Noonan syndrome-like disorder and early-onset JMML (NSLL; 613563), Niemeyer et al. (2010) identified a heterozygous germline mutation in the CBL gene, resulting in a cys396-to-arg (C396R) substitution. Leukemic cells were homozygous for the mutation. The patient had developmental delay and hearing loss, but also developed optic atrophy, hypertension, and cardiomyopathy, consistent with vascular pathology. Niemeyer et al. (2010) postulated that the CBL mutation contributed to dysregulated lymphocyte signaling and vasculitis.

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

Last Updated: Sep 29, 2024