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NM_001042492.3(NF1):c.4600C>T (p.Arg1534Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 15, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000492716.9

Allele description [Variation Report for NM_001042492.3(NF1):c.4600C>T (p.Arg1534Ter)]

NM_001042492.3(NF1):c.4600C>T (p.Arg1534Ter)

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.4600C>T (p.Arg1534Ter)
HGVS:
  • NC_000017.11:g.31261733C>T
  • NG_009018.1:g.171757C>T
  • NM_000267.3:c.4537C>T
  • NM_001042492.3:c.4600C>TMANE SELECT
  • NP_000258.1:p.Arg1513Ter
  • NP_001035957.1:p.Arg1534Ter
  • NP_001035957.1:p.Arg1534Ter
  • LRG_214t1:c.4537C>T
  • LRG_214t2:c.4600C>T
  • LRG_214:g.171757C>T
  • LRG_214p1:p.Arg1513Ter
  • LRG_214p2:p.Arg1534Ter
  • NC_000017.10:g.29588751C>T
  • NM_001042492.2:c.4600C>T
  • NM_001042492.3:c.4600C>T
  • p.Arg1513*
Protein change:
R1513*
Links:
dbSNP: rs760703505
NCBI 1000 Genomes Browser:
rs760703505
Molecular consequence:
  • NM_000267.3:c.4537C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001042492.3:c.4600C>T - nonsense - [Sequence Ontology: SO:0001587]
Functional consequence:
protein truncation [Variation Ontology: 0015]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000581282Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))		Pathogenic
(Jan 18, 2016) 		germlineclinical testing

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

Citation Link,

SCV002527577Sema4, Sema4
criteria provided, single submitter

(Sema4 Curation Guidelines)		Pathogenic
(Sep 15, 2021) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing, curation

Citations

PubMed

Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1.

Ko JM, Sohn YB, Jeong SY, Kim HJ, Messiaen LM.

Pediatr Neurol. 2013 Jun;48(6):447-53. doi: 10.1016/j.pediatrneurol.2013.02.004.

PubMed [citation]
PMID:
23668869

Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders.

Side L, Taylor B, Cayouette M, Conner E, Thompson P, Luce M, Shannon K.

N Engl J Med. 1997 Jun 12;336(24):1713-20.

PubMed [citation]
PMID:
9180088
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000581282.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.R1534* pathogenic mutation (also known as c.4600C>T), located in coding exon 35 of the NF1 gene, results from a C to T substitution at nucleotide position 4600. This changes the amino acid from an arginine to a stop codon within coding exon 35. This mutation has been observed in multiple neurofibromatosis type 1 (NF1) families,<span style="background-color:initial">including one family in which the mutation segregated with NF1 in a proband diagnosed with juvenile myelomonocytic leukemia at 14 months and his affected mother (<span style="background-color:initial">Ko JMet al. Pediatr. Neurol. 2013 Jun;48(6):447-53,Side Let al. N. Engl. J. Med. 1997 Jun;336(24):1713-20; ​DuatRodriguez A et al.AnPediatr(Barc). 2015 Sep;83(3):173-82<span style="background-color:initial">). In addition to the clinical information presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).<span style="background-color:initial">This mutation is also known as p.R1513* (c.4537C>T) in published literature.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Sema4, Sema4, SCV002527577.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024