NM_001042492.3(NF1):c.3579T>A (p.Phe1193Leu) AND Neurofibromatosis, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 2, 2022
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:: RCV002471613.2

Allele description [Variation Report for NM_001042492.3(NF1):c.3579T>A (p.Phe1193Leu)]

NM_001042492.3(NF1):c.3579T>A (p.Phe1193Leu)

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.3579T>A (p.Phe1193Leu)

HGVS:

NC_000017.11:g.31233084T>A
NG_009018.1:g.143108T>A
NM_000267.4:c.3579T>A
NM_001042492.3:c.3579T>AMANE SELECT
NP_000258.1:p.Phe1193Leu
NP_000258.1:p.Phe1193Leu
NP_001035957.1:p.Phe1193Leu
NP_001035957.1:p.Phe1193Leu
LRG_214t1:c.3579T>A
LRG_214t2:c.3579T>A
LRG_214:g.143108T>A
LRG_214p1:p.Phe1193Leu
LRG_214p2:p.Phe1193Leu
NC_000017.10:g.29560102T>A
NM_000267.3:c.3579T>A
NM_001042492.2:c.3579T>A

Protein change:

F1193L

Links:

dbSNP: rs2067142728

NCBI 1000 Genomes Browser:

rs2067142728

Molecular consequence:

NM_000267.4:c.3579T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042492.3:c.3579T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neurofibromatosis, type 1 (NF1)
Synonyms:: NEUROFIBROMATOSIS, TYPE I; VON RECKLINGHAUSEN DISEASE; NEUROFIBROMATOSIS, TYPE I, SOMATIC; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002769016	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11735023, 23244495, 34080803, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002769016

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 2, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 ( NF1) gene.

Han SS, Cooper DN, Upadhyaya MN.

Hum Genet. 2001 Nov;109(5):487-97. Epub 2001 Oct 11.

PubMed [citation]

PMID:: 11735023

Genotype-phenotype associations in neurofibromatosis type 1 (NF1): an increased risk of tumor complications in patients with NF1 splice-site mutations?

Alkindy A, Chuzhanova N, Kini U, Cooper DN, Upadhyaya M.

Hum Genomics. 2012 Aug 13;6(1):12. doi: 10.1186/1479-7364-6-12.

PubMed [citation]

PMID:: 23244495
PMCID:: PMC3528442

See all PubMed Citations (4)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002769016.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with NF1-related conditions. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. A child may be more severely affected than a carrier parent (GeneReviews). (I) 0200 - Variant is predicted to result in a missense amino acid change from phenylalanine to leucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated tubulin binding domain (PMID:34080803). (I) 0702 - Other missense variants comparable to the one identified in this case have strong previous evidence for pathogenicity. At least three alternative amino acid changes have been reported as pathogenic in unrelated individuals with NF1-related conditions, including one de novo report (Clinvar, DECIPHER, PMID:23244495, 11735023). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual with neurofibromatosis type 1 (ClinVar, PMID:34080803). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Aug 9, 2025

ClinVar

Relating variation to medicine