NM_001042492.3(NF1):c.1660C>T (p.Gln554Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 10, 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:: RCV000756430.9

Allele description [Variation Report for NM_001042492.3(NF1):c.1660C>T (p.Gln554Ter)]

NM_001042492.3(NF1):c.1660C>T (p.Gln554Ter)

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.1660C>T (p.Gln554Ter)

HGVS:

NC_000017.11:g.31221868C>T
NG_009018.1:g.131892C>T
NM_000267.3:c.1660C>T
NM_001042492.3:c.1660C>TMANE SELECT
NM_001128147.3:c.1660C>T
NP_000258.1:p.Gln554Ter
NP_001035957.1:p.Gln554Ter
NP_001121619.1:p.Gln554Ter
LRG_214t1:c.1660C>T
LRG_214:g.131892C>T
LRG_214p1:p.Gln554Ter
NC_000017.10:g.29548886C>T
NM_001042492.3:c.1660C>T
p.Gln554*

Protein change:

Q554*

Links:

dbSNP: rs953440640

NCBI 1000 Genomes Browser:

rs953440640

Molecular consequence:

NM_000267.3:c.1660C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001042492.3:c.1660C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001128147.3:c.1660C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000884248	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Jun 7, 2017)	germline	clinical testing	Citation Link,
SCV004169797	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000884248

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Jun 7, 2017)

germline

clinical testing

Citation Link,

SCV004169797

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 10, 2023)

germline

clinical testing

Citation Link

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884248.1

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

Description

The NF1 c.1660C>T;p.Gln554Ter variant is listed as pathogenic in a gene-specific database in two individuals (see link below). Additionally, according to a personal communication with the Human Gene Mutation Database, this variant was also included in van Minkelen 2014. The variant is not listed in the ClinVar database, the dbSNP variant database, or in the general population-based databases (Exome Variant Server, Genome Aggregation Database). This variant introduces a premature termination codon and is predicted to result in a truncated or absent protein. Considering available information, this variant is classified as pathogenic. References: Link to NF1 database: https://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=NF1 van Minkelen R et al. A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands. Clin Genet. 2014 Apr;85(4):318-27.

#	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 GeneDx, SCV004169797.1

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in a patient in the published literature; however, this patient's phenotype was not described (Cho et al., 2017); This variant is associated with the following publications: (PMID: 23656349, 28851938)

#	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: Feb 14, 2024

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