NM_001042492.3(NF1):c.3232dup (p.Ser1078fs) AND Neurofibromatosis, type 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 31, 2023
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:: RCV001384142.6

Allele description [Variation Report for NM_001042492.3(NF1):c.3232dup (p.Ser1078fs)]

NM_001042492.3(NF1):c.3232dup (p.Ser1078fs)

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.3232dup (p.Ser1078fs)

HGVS:

NC_000017.11:g.31232107dup
NG_009018.1:g.142131dup
NM_000267.3:c.3232dup
NM_001042492.3:c.3232dupMANE SELECT
NP_000258.1:p.Ser1078fs
NP_001035957.1:p.Ser1078fs
LRG_214t1:c.3232dup
LRG_214:g.142131dup
LRG_214p1:p.Ser1078fs
NC_000017.10:g.29559122_29559123insT
NC_000017.10:g.29559125dup
NM_000267.3:c.3232dup
NM_000267.3:c.3232dupT
NM_001042492.2:c.3232dupT

Protein change:

S1078fs

Links:

dbSNP: rs2151433720

NCBI 1000 Genomes Browser:

rs2151433720

Molecular consequence:

NM_000267.3:c.3232dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042492.3:c.3232dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001478134	Department of Pediatrics, Memorial Sloan Kettering Cancer Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 15, 2020)	germline	research	PubMed (2) [See all records that cite these PMIDs] 28873162, 25741868
SCV001583527	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 31, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21520333, 10712197, 23913538, 28492532
SCV002559939	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001478134

Department of Pediatrics, Memorial Sloan Kettering Cancer Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 15, 2020)

germline

research

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

SCV001583527

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 31, 2023)

germline

clinical testing

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

SCV002559939

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 15, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Mandelker D, Zhang L, Kemel Y, Stadler ZK, Joseph V, Zehir A, Pradhan N, Arnold A, Walsh MF, Li Y, Balakrishnan AR, Syed A, Prasad M, Nafa K, Carlo MI, Cadoo KA, Sheehan M, Fleischut MH, Salo-Mullen E, Trottier M, Lipkin SM, Lincoln A, et al.

JAMA. 2017 Sep 5;318(9):825-835. doi: 10.1001/jama.2017.11137. Erratum in: JAMA. 2018 Dec 11;320(22):2381. doi: 10.1001/jama.2018.17511.

PubMed [citation]

PMID:: 28873162
PMCID:: PMC5611881

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21520333

See all PubMed Citations (6)

Details of each submission

From Department of Pediatrics, Memorial Sloan Kettering Cancer Center, SCV001478134.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001583527.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 995899). This premature translational stop signal has been observed in individual(s) with clinical features of NF1-related conditions (PMID: 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1078Phefs*11) 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).

#	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

From Genome-Nilou Lab, SCV002559939.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine