NM_001042492.3(NF1):c.1260+1G>T AND Neurofibromatosis, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 9, 2020
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:: RCV000691582.4

Allele description [Variation Report for NM_001042492.3(NF1):c.1260+1G>T]

NM_001042492.3(NF1):c.1260+1G>T

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.1260+1G>T

HGVS:

NC_000017.11:g.31201486G>T
NG_009018.1:g.111510G>T
NM_000267.3:c.1260+1G>T
NM_001042492.3:c.1260+1G>TMANE SELECT
NM_001128147.3:c.1260+1G>T
LRG_214t1:c.1260+1G>T
LRG_214:g.111510G>T
NC_000017.10:g.29528504G>T

Links:

dbSNP: rs267606603

NCBI 1000 Genomes Browser:

rs267606603

Molecular consequence:

NM_000267.3:c.1260+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001042492.3:c.1260+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001128147.3:c.1260+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819368	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 9, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10677298, 16199547, 10712197, 23913538, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000819368

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 9, 2020)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1.

Eisenbarth I, Beyer K, Krone W, Assum G.

Am J Hum Genet. 2000 Feb;66(2):393-401.

PubMed [citation]

PMID:: 10677298
PMCID:: PMC1288091

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819368.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a donor splice site in intron 11 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10677298, Invitae). ClinVar contains an entry for this variant (Variation ID: 570670). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine