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

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 3, 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:
RCV003772177.2

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:
RASopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: C5555857

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004686106Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 3, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

In hematopoietic cells with a germline mutation of CBL, loss of heterozygosity is not a signature of juvenile myelo-monocytic leukemia.

Strullu M, Caye A, Cassinat B, Fenneteau O, Touzot F, Blauwblomme T, Rodriguez R, Latour S, Petit A, Barlogis V, Galambrun C, Leblanc T, Baruchel A, Chomienne C, Cavé H.

Leukemia. 2013 Dec;27(12):2404-7. doi: 10.1038/leu.2013.203. Epub 2013 Jul 4. No abstract available.

PubMed [citation]
PMID:
23823657

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004686106.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 418 of the CBL protein (p.Phe418Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neutrophilic dermatosis (PMID: 23823657). ClinVar contains an entry for this variant (Variation ID: 1327077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CBL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024