NM_005188.4(CBL):c.1253T>C (p.Phe418Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 25, 2023
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:: RCV004040834.1

Allele description [Variation Report for NM_005188.4(CBL):c.1253T>C (p.Phe418Ser)]

NM_005188.4(CBL):c.1253T>C (p.Phe418Ser)

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.1253T>C (p.Phe418Ser)

HGVS:

NC_000011.10:g.119278535T>C
NG_016808.1:g.77256T>C
NM_005188.4:c.1253T>CMANE SELECT
NP_005179.2:p.Phe418Ser
LRG_608t1:c.1253T>C
LRG_608:g.77256T>C
NC_000011.9:g.119149245T>C
NM_005188.2:c.1253T>C
NM_005188.3:c.1253T>C

Protein change:

F418S

Links:

dbSNP: rs772156285

NCBI 1000 Genomes Browser:

rs772156285

Molecular consequence:

NM_005188.4:c.1253T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005022931	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 25, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 20555362, 20644105, 20880116, 21681191, 22131879, 22733026, 23823657, 33897294, 35236052 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005022931

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 25, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Gain of CBL-interacting protein, a possible alternative to CBL mutations in myeloid malignancies.

Adélaïde J, Gelsi-Boyer V, Rocquain J, Carbuccia N, Birnbaum DJ, Finetti P, Bertucci F, Mozziconacci MJ, Vey N, Birnbaum D, Chaffanet M.

Leukemia. 2010 Aug;24(8):1539-41. doi: 10.1038/leu.2010.135. Epub 2010 Jun 17. No abstract available.

PubMed [citation]

PMID:: 20555362

Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1.

Kohlmann A, Grossmann V, Klein HU, Schindela S, Weiss T, Kazak B, Dicker F, Schnittger S, Dugas M, Kern W, Haferlach C, Haferlach T.

J Clin Oncol. 2010 Aug 20;28(24):3858-65. doi: 10.1200/JCO.2009.27.1361. Epub 2010 Jul 19.

PubMed [citation]

PMID:: 20644105

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV005022931.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The p.F418S variant (also known as c.1253T>C), located in coding exon 9 of the CBL gene, results from a T to C substitution at nucleotide position 1253. The phenylalanine at codon 418 is replaced by serine, an amino acid with highly dissimilar properties. This variant has been detected in individuals with hematological disorders or myelodysplastic/myeloproliferative neoplasms (Kohlmann A et al. J Clin Oncol, 2010 Aug;28:3858-65; Adélaïde J et al. Leukemia, 2010 Aug;24:1539-41; Kao HW et al. Neoplasia, 2011 Nov;13:1035-42; Schnittger S et al. Haematologica, 2012 Dec;97:1890-4; Bogucka-Fedorczuk A et al. Cent Eur J Immunol, 2021 Apr;46:121-126). This variant was detected homozygous in peripheral blood cells and neutrophils infiltrating a cutaneous lesion, and heterozygous in fibroblasts from an individual with growth delay and dysmorphic features who developed neutrophilic dermatosis; the proband's mother and sibling were heterozygous for the variant in peripheral blood and were not indicated as affected (Strullu M et al. Leukemia, 2013 Dec;27:2404-7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 7, 2024

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