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NM_001042492.3(NF1):c.2218G>T (p.Glu740Ter) AND Neurofibromatosis, type 1

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
May 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:
RCV000497183.3

Allele description [Variation Report for NM_001042492.3(NF1):c.2218G>T (p.Glu740Ter)]

NM_001042492.3(NF1):c.2218G>T (p.Glu740Ter)

Gene:
NF1:neurofibromin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q11.2
Genomic location:
Preferred name:
NM_001042492.3(NF1):c.2218G>T (p.Glu740Ter)
HGVS:
  • NC_000017.11:g.31226651G>T
  • NG_009018.1:g.136675G>T
  • NM_000267.3:c.2218G>T
  • NM_001042492.3:c.2218G>TMANE SELECT
  • NP_000258.1:p.Glu740Ter
  • NP_001035957.1:p.Glu740Ter
  • NP_001035957.1:p.Glu740Ter
  • LRG_214t1:c.2218G>T
  • LRG_214t2:c.2218G>T
  • LRG_214:g.136675G>T
  • LRG_214p1:p.Glu740Ter
  • LRG_214p2:p.Glu740Ter
  • NC_000017.10:g.29553669G>T
  • NM_001042492.2:c.2218G>T
Protein change:
E740*
Links:
dbSNP: rs1135402827
NCBI 1000 Genomes Browser:
rs1135402827
Molecular consequence:
  • NM_000267.3:c.2218G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001042492.3:c.2218G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Neurofibromatosis, type 1 (NF1)
Synonyms:
NEUROFIBROMATOSIS, TYPE I; Recklinghausen's disease; Von Recklinghausen disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000588742Medical Genetics, University of Parma
no assertion criteria provided
Pathogenic
(Feb 2, 2017)
germlineclinical testing

SCV004538953Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(May 25, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Patterns of Novel Alleles and Genotype/Phenotype Correlations Resulting from the Analysis of 108 Previously Undetected Mutations in Patients Affected by Neurofibromatosis Type I.

Bonatti F, Adorni A, Matichecchia A, Mozzoni P, Uliana V, Pisani F, Garavelli L, Graziano C, Gnoli M, Carli D, Bigoni S, Boschi E, Martorana D, Percesepe A.

Int J Mol Sci. 2017 Sep 29;18(10). doi:pii: E2071. 10.3390/ijms18102071.

PubMed [citation]
PMID:
28961165
PMCID:
PMC5666753

Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain.

Fahsold R, Hoffmeyer S, Mischung C, Gille C, Ehlers C, Kücükceylan N, Abdel-Nour M, Gewies A, Peters H, Kaufmann D, Buske A, Tinschert S, Nürnberg P.

Am J Hum Genet. 2000 Mar;66(3):790-818.

PubMed [citation]
PMID:
10712197
PMCID:
PMC1288164
See all PubMed Citations (4)

Details of each submission

From Medical Genetics, University of Parma, SCV000588742.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004538953.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 431604). This premature translational stop signal has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 28961165). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu740*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538).

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

Last Updated: Sep 29, 2024