PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic/Likely pathogenic, drug response
- Review status:
- reviewed by expert panel
- Submissions:
- 5 (Most recent: Oct 19, 2021)
- Last evaluated:
- Jul 31, 2020
- Accession:
- VCV000054006.4
- Variation ID:
- 54006
- Description:
- single nucleotide variant
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NM_000492.4(CFTR):c.577G>A (p.Glu193Lys)
- Allele ID
- 68673
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 7q31.2
- Genomic location
- 7: 117534363 (GRCh38) GRCh38 UCSC
- 7: 117174417 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceP13569:p.Glu193Lys NM_000492.3:c.577G>A NP_000483.3:p.Glu193Lys missense NC_000007.13:g.117174417G>A NC_000007.14:g.117534363G>A NG_016465.4:g.73580G>A NM_000492.4:c.577G>A MANE Select NP_000483.3:p.Glu193Lys missense LRG_663:g.73580G>A LRG_663t1:c.577G>A LRG_663p1:p.Glu193Lys - Protein change
- E193K
- Other names
- -
- Canonical SPDI
- NC_000007.14:117534362:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
- ClinGen: CA327578
- UniProtKB: P13569#VAR_000132
- dbSNP: rs397508759
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 4 | reviewed by expert panel | Jul 31, 2020 | RCV000577109.3 | |
| drug response | 1 | reviewed by expert panel | Mar 22, 2018 | RCV000660831.2 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | Supporting information
(See all) |
|---|---|---|---|---|
|
drug response
(Mar 22, 2018)
|
reviewed by expert panel
Method: curation
|
ivacaftor response - Efficacy
Drug used for
Cystic Fibrosis
Allele origin:
germline
|
PharmGKB
Accession: SCV000783070.1
Submitted: (Jun 18, 2018)
Comment:
Drug is not necessarily used to treat response condition
|
Comment:
PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or … (more)
PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system. (less)
|
|
Pathogenic
(Jul 31, 2020)
|
reviewed by expert panel
Method: research
|
Cystic fibrosis
Allele origin:
germline
|
CFTR2
Accession: SCV001981553.1
Submitted: (Oct 19, 2021) |
|
|
Pathogenic
(Nov 05, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
Allele origin:
unknown
|
Mendelics
Accession: SCV000886299.1
Submitted: (Nov 11, 2018) |
|
|
Likely pathogenic
(Jul 10, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
Allele origin:
germline
|
Invitae
Accession: SCV001577106.1
Submitted: (Jan 07, 2021) |
Comment:
This sequence change replaces glutamic acid with lysine at codon 193 of the CFTR protein (p.Glu193Lys). The glutamic acid residue is moderately conserved and there … (more)
This sequence change replaces glutamic acid with lysine at codon 193 of the CFTR protein (p.Glu193Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with cystic fibrosis or congenital bilateral absence of the vas deferrens (PMID: 7544319, 7529962). ClinVar contains an entry for this variant (Variation ID: 54006). This variant has been reported to affect CFTR protein function (PMID: 9305991, 23891399, 19491324). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
|
|
not provided
(-)
|
no assertion provided
Method: literature only
|
CFTR-related disorders
Allele origin:
germline
|
ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000679503.1
Submitted: (Mar 30, 2013) |
|
Functional evidence
Help| 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 this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. | Van Goor F | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2014 | PMID: 23891399 |
| Mutation-specific potency and efficacy of cystic fibrosis transmembrane conductance regulator chloride channel potentiators. | Caputo A | The Journal of pharmacology and experimental therapeutics | 2009 | PMID: 19491324 |
| Disease-associated mutations in cytoplasmic loops 1 and 2 of cystic fibrosis transmembrane conductance regulator impede processing or opening of the channel. | Seibert FS | Biochemistry | 1997 | PMID: 9305991 |
| Search for mutations in pancreatic sufficient cystic fibrosis Italian patients: detection of 90% of molecular defects and identification of three novel mutations. | Brancolini V | Human genetics | 1995 | PMID: 7544319 |
| Is congenital bilateral absence of vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients. | Mercier B | American journal of human genetics | 1995 | PMID: 7529962 |
| https://cftr2.org | - | - | - | - |
| https://www.pharmgkb.org/clinicalAnnotation/1449191424 | - | - | - | - |
Text-mined citations for rs397508759...
HelpThese 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 Oct 21, 2021