ClinVar Genomic variation as it relates to human health
NM_001042492.3(NF1):c.1A>G (p.Met1Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001042492.3(NF1):c.1A>G (p.Met1Val)
Variation ID: 404429 Accession: VCV000404429.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q11.2 17: 31095310 (GRCh38) [ NCBI UCSC ] 17: 29422328 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 17, 2017 Feb 20, 2024 Dec 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001042492.3:c.1A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001035957.1:p.Met1Val missense initiator codon variant NM_000267.3:c.1A>G NP_000258.1:p.Met1Val missense initiator codon variant NM_001128147.3:c.1A>G NP_001121619.1:p.Met1Val missense initiator codon variant NC_000017.11:g.31095310A>G NC_000017.10:g.29422328A>G NG_009018.1:g.5334A>G NG_056197.1:g.1806A>G LRG_214:g.5334A>G LRG_214t1:c.1A>G LRG_214p1:p.Met1Val - Protein change
- M1V
- Other names
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- Canonical SPDI
- NC_000017.11:31095309:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NF1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
13559 | 13966 | |
LOC111811965 | - | - | - |
GRCh38 GRCh38 |
- | 187 |
MIR4733HG | - | - | - |
GRCh38 GRCh38 |
- | 198 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Dec 16, 2023 | RCV000476863.13 | |
Pathogenic (3) |
criteria provided, single submitter
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Oct 28, 2022 | RCV001556803.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 28, 2021 | RCV002418350.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 26, 2020)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 1
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV001479044.2
First in ClinVar: Feb 13, 2021 Last updated: Sep 03, 2023 |
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Pathogenic
(Feb 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 1
Affected status: yes
Allele origin:
germline
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Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University
Accession: SCV001571441.2
First in ClinVar: Apr 22, 2021 Last updated: Sep 03, 2023 |
Number of individuals with the variant: 1
Ethnicity/Population group: Japanese
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Pathogenic
(Jun 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001653524.2
First in ClinVar: Jun 08, 2021 Last updated: Sep 03, 2023 |
Comment:
This variant has been found in a 4-year-old girl with multiple Cafe-au-lait spots.
Age: 0-9 years
Sex: female
Ethnicity/Population group: Persian
Geographic origin: Iran
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Pathogenic
(Mar 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002561534.2
First in ClinVar: Aug 23, 2022 Last updated: Sep 03, 2023 |
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Pathogenic
(Sep 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002724204.2
First in ClinVar: Nov 29, 2022 Last updated: Sep 03, 2023 |
Comment:
The p.M1? pathogenic mutation (also known as c.1A>G) is located in coding exon 1 of the NF1 gene and results from a A to G … (more)
The p.M1? pathogenic mutation (also known as c.1A>G) is located in coding exon 1 of the NF1 gene and results from a A to G substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). This alteration has been reported in several individuals with a clinical diagnosis of neurofibromatosis type 1 (NF1) (Brinckmann A et al. Electrophoresis, 2007 Dec;28:4295-301; Ko JM et al. Pediatr. Neurol., 2013 Jun;48:447-53; Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8; Tsipi M et al. J Neurol Sci. 2018 Dec 15;395:95-105; Kang E et al. J Hum Genet. 2020 Jan;65(2):79-89). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Oct 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001778446.4
First in ClinVar: Aug 13, 2021 Last updated: Sep 03, 2023 |
Comment:
Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is … (more)
Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30308447, 23668869, 18041031, 23913538, 31776437, 20844836) (less)
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Pathogenic
(Dec 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000541981.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects the initiator methionine of the NF1 mRNA. The next in-frame methionine is located at codon 68. This variant is not present … (more)
This sequence change affects the initiator methionine of the NF1 mRNA. The next in-frame methionine is located at codon 68. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with neurofibromatosis type 1 (PMID: 23668869, 23913538). ClinVar contains an entry for this variant (Variation ID: 404429). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037371.2 First in ClinVar: Dec 21, 2021 Last updated: Sep 03, 2023 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002038347.2 First in ClinVar: Dec 21, 2021 Last updated: Sep 03, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types. | Kang E | Journal of human genetics | 2020 | PMID: 31776437 |
Phenotypic expression of a spectrum of Neurofibromatosis Type 1 (NF1) mutations identified through NGS and MLPA. | Tsipi M | Journal of the neurological sciences | 2018 | PMID: 30308447 |
NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: the French experience. | Sabbagh A | Human mutation | 2013 | PMID: 23913538 |
Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1. | Ko JM | Pediatric neurology | 2013 | PMID: 23668869 |
Detection of novel NF1 mutations and rapid mutation prescreening with Pyrosequencing. | Brinckmann A | Electrophoresis | 2007 | PMID: 18041031 |
Text-mined citations for rs1060500252 ...
HelpRecord last updated Feb 28, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.