NM_000492.3(CFTR):c.617T>G (p.Leu206Trp) AND Cystic fibrosis

Clinical significance:Pathogenic (Last evaluated: Mar 28, 2013)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
6 submissions [Details]
Record status:
current
Accession:
RCV000007611.8

Allele description

NM_000492.3(CFTR):c.617T>G (p.Leu206Trp)

Gene:
CFTR:cystic fibrosis transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.3(CFTR):c.617T>G (p.Leu206Trp)
HGVS:
  • NC_000007.14:g.117535285T>G
  • NG_016465.4:g.74502T>G
  • NM_000492.3:c.617T>G
  • NP_000483.3:p.Leu206Trp
  • NC_000007.13:g.117175339T>G
  • NG_016465.1:g.60323T>G
  • P13569:p.Leu206Trp
Protein change:
L206W; LEU206TRP
Links:
UniProtKB: P13569#VAR_000136; OMIM: 602421.0084; dbSNP: rs121908752
NCBI 1000 Genomes Browser:
rs121908752
Allele Frequency:
0.00022(G), GO-ESP
Molecular consequence:
  • NM_000492.3:c.617T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
5

Condition(s)

Name:
Cystic fibrosis (CF)
Identifiers:
MedGen: C0010674; Orphanet: 586; OMIM: 219700
Age of onset:
All ages
Prevalence:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000027812OMIMno assertion criteria providedPathogenic
(Apr 1, 2005)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000071508CFTR2 - CFTR2reviewed by expert panel
pathogenic
(Mar 28, 2013)
germlinecuration

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

Citation Link,

SCV000075234Invitae no assertion providednot providedgermlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000231548Emory Genetics Laboratory,Emory Universitycriteria provided, single submitter
Pathogenic
(Oct 12, 2015)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000485228Counsylcriteria provided, single submitter
Pathogenic
(Feb 2, 2016)
unknownclinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000536746Division of Human Genetics,Children's Hospital of Philadelphia - CSER-PediSeqno assertion criteria providedPathogenic
(Apr 21, 2016)
germlineresearch

PubMed (10)
[See all records that cite these PMIDs]

Description

Mutation analysis was conducted as part of the CFTR2 project and found: - patients carrying the mutation in trans with another CF-causing mutation had an average sweat chloride >60 mEq/L - testing of the mutation in a cell-based system indicated <10% function when compared to wild-type - no evidence of non-penetrance of the mutation This detailed medical and genetics information is complicated and potentially confusing. We encourage you to discuss this information with your doctor, a genetic counselor, or a CF specialist. The information shown is for educational purposes only and is not intended for diagnostic use. You should not make any medical or reproductive decisions or change your health behaviour based on this information without talking to your doctor. To find a genetic counselor near you, please visit http://www.nsgc.org. To find a CF care center near you, please visit http://cftr2.org.

SCV000071508

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknown5not providednot providednot providednot providedclinical testing, research
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

L206W mutation of the cystic fibrosis gene, relatively frequent in French Canadians, is associated with atypical presentations of cystic fibrosis.

Rozen R, Ferreira-Rajabi L, Robb L, Colman N.

Am J Med Genet. 1995 Jul 3;57(3):437-9.

PubMed [citation]
PMID:
7545869

Misprocessing of the CFTR protein leads to mild cystic fibrosis phenotype.

Clain J, Lehmann-Che J, Duguépéroux I, Arous N, Girodon E, Legendre M, Goossens M, Edelman A, de Braekeleer M, Teulon J, Fanen P.

Hum Mutat. 2005 Apr;25(4):360-71.

PubMed [citation]
PMID:
15776432
See all PubMed Citations (15)

Details of each submission

From OMIM, SCV000027812.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

The leu206-to-trp (L206W) mutation of the CFTR gene was first identified in 3 CF (219700) patients from South France (Claustres et al., 1993). Rozen et al. (1995) reported that it is relatively frequent in French Canadians from Quebec. On the basis of findings in 7 French Canadian probands, they suggested that this mutation is likely to be present in patients with atypical forms of CF and may be present in otherwise healthy men and women with infertility. Their group contained 47-year-old and 48-year-old sisters and their 30-year-old brother. The women were thought to have reduced fertility and the man had absence of the vas deferentia. The man and 1 sister had normal pulmonary function and high-resolution CT scan of the chest. The 47-year-old sister had had left upper lobectomy for presumed bronchiectasis at the age of 20 years and had had frequent pulmonary infections but had surprisingly well-preserved lung function.

Clain et al. (2005) noted that the L206W mutation can result in variable disease phenotypes. Individuals bearing this mutation in trans with the severe CF-causing mutation F508del (602421.0001) may have CF or isolated congenital bilateral absence of the vas deferens (277180). Clain et al. (2005) studied the effect of the L206W mutation on CFTR protein production and function and examined the genotype-phenotype correlation of L206W/F508del compound heterozygote patients. They showed that L206W is a processing (class II) mutation, as the CFTR biosynthetic pathway was severely impaired, whereas single-channel measurements indicated ion conductance similar to the wildtype protein. These data raised the larger question of the phenotypic variability of class II mutants, including F508del. Clain et al. (2005) concluded that since multiple potential properties could modify the processing of the CFTR protein during its course to the cell surface, environmental and other genetic factors might contribute to this variability.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From CFTR2 - CFTR2, SCV000071508.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

Cystic fibrosis on the basis of clinical, functional, and penetrance analysis, as described in www.cftr2.org

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae , SCV000075234.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Emory Genetics Laboratory,Emory University, SCV000231548.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided5not providednot providednot provided

From Counsyl, SCV000485228.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Division of Human Genetics,Children's Hospital of Philadelphia - CSER-PediSeq, SCV000536746.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (10)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 12, 2017