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NM_000492.4(CFTR):c.3197G>A (p.Arg1066His) AND not specified

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 20, 2017
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000506781.16

Allele description [Variation Report for NM_000492.4(CFTR):c.3197G>A (p.Arg1066His)]

NM_000492.4(CFTR):c.3197G>A (p.Arg1066His)

Genes:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC111674472:DNase I hypersensitive sites in introns 16 and 17a of CFTR [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.4(CFTR):c.3197G>A (p.Arg1066His)
HGVS:
  • NC_000007.14:g.117611638G>A
  • NG_016465.4:g.150855G>A
  • NG_056128.2:g.4692G>A
  • NM_000492.4:c.3197G>AMANE SELECT
  • NP_000483.3:p.Arg1066His
  • NP_000483.3:p.Arg1066His
  • LRG_663t1:c.3197G>A
  • LRG_663:g.150855G>A
  • LRG_663p1:p.Arg1066His
  • NC_000007.13:g.117251692G>A
  • NG_056128.1:g.4692G>A
  • NM_000492.3:c.3197G>A
  • P13569:p.Arg1066His
Protein change:
R1066H; ARG1066HIS
Links:
UniProtKB: P13569#VAR_000237; OMIM: 602421.0054; dbSNP: rs121909019
NCBI 1000 Genomes Browser:
rs121909019
Molecular consequence:
  • NM_000492.4:c.3197G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000603049ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Pathogenic
(Apr 14, 2017) 		germlineclinical testing

Citation Link,

SCV000917195Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Nov 20, 2017) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function.

Van Goor F, Yu H, Burton B, Hoffman BJ.

J Cyst Fibros. 2014 Jan;13(1):29-36. doi: 10.1016/j.jcf.2013.06.008. Epub 2013 Jul 23.

PubMed [citation]
PMID:
23891399

Detection of over 98% cystic fibrosis mutations in a Celtic population.

Férec C, Audrezet MP, Mercier B, Guillermit H, Moullier P, Quere I, Verlingue C.

Nat Genet. 1992 Jun;1(3):188-91.

PubMed [citation]
PMID:
1284639
See all PubMed Citations (3)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000603049.1

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917195.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: The CFTR c.3197G>A (p.Arg1066His) variant involves the alteration of a conserved nucleotide, is predicted to be damaging by 5/5 in silico tools and is located in ABC transporter type 1 domain of the protein (InterPro). This variant was found in 9/276618 control chromosomes (gnomAD) at a frequency of 0.0000325, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported in many CF patients in literature and clinical databases. Functional studies showed this variant causes severe CFTR maturation defect as well as chloride transport defect (Sosnay_2013, Van Goor_2013). Multiple clinical laboratories/reputable databases have classified this variant as pathogenic. In addition, this codon is a known hot spot for mutations (R1066L, R1066P, R1066S and R1066C) which are found in patients with CF and CF-related phenotypes. Taken together, this variant was classified as pathogenic.

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

Last Updated: Oct 13, 2024