VCV000217851.1 - ClinVar

NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu)

Germline

Classification

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.

(5)

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.

Pathogenic/Likely pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu)

Variation ID: 217851 Accession: VCV000217851.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p23.2 2: 29220829 (GRCh38) [ NCBI UCSC ] 2: 29443695 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Nov 14, 2015	Mar 8, 2017	Mar 10, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_004304.5:c.3522C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004295.2:p.Phe1174Leu	missense
NM_001353765.2:c.318C>A	NP_001340694.1:p.Phe106Leu	missense
NC_000002.12:g.29220829G>T
NC_000002.11:g.29443695G>T
NG_009445.1:g.705738C>A
LRG_488:g.705738C>A
	Q9UM73:p.Phe1174Leu

... more HGVS ... less HGVS

Protein change

F1174L, F106L

Other names

Canonical SPDI

NC_000002.12:29220828:G:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA279586 UniProtKB: Q9UM73#VAR_063857 dbSNP: rs863225281 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help 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.
ALK		No evidence available	No evidence available	GRCh38 GRCh37	5133	5173

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 Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Neuroblastoma, susceptibility to, 3	Pathogenic (1)	no assertion criteria provided	Oct 7, 2015	RCV000201882.2
Non-small cell lung carcinoma	not provided (1)	no classification provided	Mar 10, 2016	RCV000418576.1
Lung adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	Dec 26, 2014	RCV000426846.1
Benign Soft Tissue Neoplasm of Uncertain Differentiation	not provided (1)	no classification provided	Mar 10, 2016	RCV000435780.1
Neuroblastoma	Pathogenic (1)	no assertion criteria provided	Mar 10, 2016	RCV000444781.1

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 Help 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 Help 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.
Pathogenic (Oct 07, 2015)	no assertion criteria provided Method: clinical testing	Neuroblastoma, susceptibility to, 3 Affected status: yes Allele origin: somatic	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia Accession: SCV000256816.1 First in ClinVar: Nov 14, 2015 Last updated: Nov 14, 2015 Comment: Clinical Testing	Number of individuals with the variant: 15
Likely pathogenic (Dec 26, 2014)	no assertion criteria provided Method: literature only	None (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503777.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (2) PubMed: 22277784‚ 24327273 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000389048:c.3522C>A
Pathogenic (Mar 10, 2016)	no assertion criteria provided Method: literature only	Neuroblastoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503776.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (5) PubMed: 21575866‚ 21838707‚ 22072639‚ 18923525‚ 21948233 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000389048:c.3522C>A
not provided (Mar 10, 2016)	no classification provided Method: literature only	Non-small cell lung carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503779.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 21030459 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000389048:c.3522C>A
not provided (Mar 10, 2016)	no classification provided Method: literature only	Benign Soft Tissue Neoplasm of Uncertain Differentiation (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000503778.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 21030459 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000389048:c.3522C>A

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

Title	Author	Journal	Year	Link
Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance.	Chen Z	Clinical cancer research : an official journal of the American Association for Cancer Research	2014	PMID: 24327273
Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.	Katayama R	Science translational medicine	2012	PMID: 22277784
Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma.	Bresler SC	Science translational medicine	2011	PMID: 22072639
ALK mutations conferring differential resistance to structurally diverse ALK inhibitors.	Heuckmann JM	Clinical cancer research : an official journal of the American Association for Cancer Research	2011	PMID: 21948233
Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684.	Schönherr C	The Biochemical journal	2011	PMID: 21838707
CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant.	Sakamoto H	Cancer cell	2011	PMID: 21575866
The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers.	Sasaki T	Cancer research	2010	PMID: 21030459
Activating mutations in ALK provide a therapeutic target in neuroblastoma.	George RE	Nature	2008	PMID: 18923525
http://docm.genome.wustl.edu/variants/ENST00000389048:c.3522C>A	-	-	-	-

Text-mined citations for rs863225281 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 08, 2024

ClinVar Genomic variation as it relates to human health

NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs863225281 ...