NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg) AND ivacaftor response - Efficacy - ClinVar

NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg) AND ivacaftor response - Efficacy

Germline classification:: drug response (1 submission)
Last evaluated:: Mar 24, 2021
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000211129.5

Allele description [Variation Report for NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg)]

NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg)

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC111674475:CFTR intron 11 enhancer [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.1647T>G (p.Ser549Arg)

Other names:

S549R (T->G)

HGVS:

NC_000007.14:g.117587801T>G
NG_016465.4:g.127018T>G
NG_056131.3:g.756T>G
NM_000492.4:c.1647T>GMANE SELECT
NP_000483.3:p.Ser549Arg
NP_000483.3:p.Ser549Arg
LRG_663t1:c.1647T>G
LRG_663:g.127018T>G
LRG_663p1:p.Ser549Arg
NC_000007.13:g.117227855T>G
NG_056131.1:g.125T>G
NM_000492.3:c.1647T>G
P13569:p.Ser549Arg

Protein change:

S549R; SER549ARG

Links:

PharmGKB: 1183960775; PharmGKB: 1183960775PA165950341; PharmGKB Clinical Annotation: 1183960775; UniProtKB: P13569#VAR_000178; OMIM: 602421.0012; dbSNP: rs121909005

NCBI 1000 Genomes Browser:

rs121909005

Molecular consequence:

NM_000492.4:c.1647T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ivacaftor response - Efficacy
Identifiers:: MedGen: CN322735

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000268176	PharmGKB	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine)	drug response (Mar 24, 2021) Condition: ivacaftor response - Efficacy Drug reported used for: Cystic Fibrosis	germline	curation	PubMed (4) [See all records that cite these PMIDs] 22293084, 25266159, 26474553, 22992668 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000268176

PharmGKB

reviewed by expert panel

(Pharmacogenomics knowledge for personalized medicine)

drug response
(Mar 24, 2021)
Condition: ivacaftor response - Efficacy
Drug reported used for: Cystic Fibrosis

germline

curation

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

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	curation

Citations

PubMed

Ivacaftor potentiation of multiple CFTR channels with gating mutations.

Yu H, Burton B, Huang CJ, Worley J, Cao D, Johnson JP Jr, Urrutia A, Joubran J, Seepersaud S, Sussky K, Hoffman BJ, Van Goor F.

J Cyst Fibros. 2012 May;11(3):237-45. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30.

PubMed [citation]

PMID:: 22293084

Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation.

De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, Higgins M.

J Cyst Fibros. 2014 Dec;13(6):674-80. doi: 10.1016/j.jcf.2014.09.005. Epub 2014 Sep 26.

PubMed [citation]

PMID:: 25266159

See all PubMed Citations (4)

Details of each submission

From PharmGKB, SCV000268176.4

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

Description

PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.

#	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: Jun 17, 2024

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