NM_001042492.3(NF1):c.3G>A (p.Met1Ile) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 9, 2017
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:: RCV002325548.1

Allele description [Variation Report for NM_001042492.3(NF1):c.3G>A (p.Met1Ile)]

NM_001042492.3(NF1):c.3G>A (p.Met1Ile)

Genes:

MIR4733HG:MIR4733 host gene [Gene - HGNC]
LOC111811965:NF1 (neurofibromin 1) promoter region [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.3G>A (p.Met1Ile)

HGVS:

NC_000017.11:g.31095312G>A
NG_009018.1:g.5336G>A
NG_056197.1:g.1808G>A
NM_000267.3:c.3G>A
NM_001042492.3:c.3G>AMANE SELECT
NM_001128147.3:c.3G>A
NP_000258.1:p.Met1Ile
NP_001035957.1:p.Met1Ile
NP_001121619.1:p.Met1Ile
LRG_214t1:c.3G>A
LRG_214:g.5336G>A
LRG_214p1:p.Met1Ile
NC_000017.10:g.29422330G>A

Protein change:

M1I

Links:

dbSNP: rs1598173737

NCBI 1000 Genomes Browser:

rs1598173737

Molecular consequence:

NM_000267.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001042492.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001128147.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000267.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042492.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128147.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002626212	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Oct 9, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002626212

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Oct 9, 2017)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: the French experience.

Sabbagh A, Pasmant E, Imbard A, Luscan A, Soares M, Blanché H, Laurendeau I, Ferkal S, Vidaud M, Pinson S, Bellanné-Chantelot C, Vidaud D, Parfait B, Wolkenstein P.

Hum Mutat. 2013 Nov;34(11):1510-8. doi: 10.1002/humu.22392. Epub 2013 Aug 26.

PubMed [citation]

PMID:: 23913538

Details of each submission

From Ambry Genetics, SCV002626212.2

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

Description

The p.M1? variant (also known as c.3G>A), located in coding exon 1 of the NF1 gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. This alteration was detected in one individual who meets National Institute of Health Neurofibromatosis Type 1 clinical criteria (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Feb 14, 2024

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