NM_000492.4(CFTR):c.3700A>G (p.Ile1234Val) AND CFTR-related disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 4, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001831553.2

Allele description

NM_000492.4(CFTR):c.3700A>G (p.Ile1234Val)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.3700A>G (p.Ile1234Val)

HGVS:

NC_000007.14:g.117627753A>G
NG_016465.4:g.166970A>G
NM_000492.4:c.3700A>GMANE SELECT
NP_000483.3:p.Ile1234Val
NP_000483.3:p.Ile1234Val
LRG_663t1:c.3700A>G
LRG_663:g.166970A>G
LRG_663p1:p.Ile1234Val
NC_000007.13:g.117267807A>G
NM_000492.3:c.3700A>G
P13569:p.Ile1234Val

Protein change:

I1234V; ILE1234VAL

Links:

UniProtKB: P13569#VAR_000254; OMIM: 602421.0110; dbSNP: rs75389940

NCBI 1000 Genomes Browser:

rs75389940

Molecular consequence:

NM_000492.4:c.3700A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CFTR-related disorder (CFTR-RD)
Synonyms:: CFTR-related disorders; CFTR-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

UNVERIFIED: Dryopteridaceae sp. ZZ-2024a voucher Rakotondrainibe F. 1705 (MO0493...
UNVERIFIED: Dryopteridaceae sp. ZZ-2024a voucher Rakotondrainibe F. 1705 (MO04932573) genomic sequence
gi|2771401432|gb|OR530080.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002075868	Natera, Inc.	no assertion criteria provided	Pathogenic (Mar 17, 2017)	germline	clinical testing
SCV004115658	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002075868

Natera, Inc.

no assertion criteria provided

Pathogenic
(Mar 17, 2017)

germline

clinical testing

SCV004115658

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Natera, Inc., SCV002075868.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV004115658.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The CFTR c.3700A>G variant is predicted to result in the amino acid substitution p.Ile1234Val. This variant has been reported in numerous patients with cystic fibrosis or CFTR-associated phenotypes (Hirtz et al. 2004. PubMed ID: 15480987; Wei et al. 2006. PubMed ID: 16617247; Molinski et al. 2014. PubMed ID: 24556927; El Bar Aluma et al. 2020. PubMed ID: 32843167). Functional studies showed that this variant alters splicing by activating an alternative splice site leading to a deletion of six amino acids and impacts protein function (Hirtz et al. 2004. PubMed ID: 15480987; Molinski et al. 2014. PubMed ID: 24556927; Ramalho et al. 2016. PubMed ID: 25735457). This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-117267807-A-G). This variant is interpreted as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine