NM_000492.4(CFTR):c.2813T>G (p.Val938Gly) AND CFTR-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 18, 2021
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:: RCV002284180.9

Allele description [Variation Report for NM_000492.4(CFTR):c.2813T>G (p.Val938Gly)]

NM_000492.4(CFTR):c.2813T>G (p.Val938Gly)

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.2813T>G (p.Val938Gly)

HGVS:

NC_000007.14:g.117603687T>G
NG_016465.4:g.142904T>G
NM_000492.4:c.2813T>GMANE SELECT
NP_000483.3:p.Val938Gly
NP_000483.3:p.Val938Gly
LRG_663t1:c.2813T>G
LRG_663:g.142904T>G
LRG_663p1:p.Val938Gly
NC_000007.13:g.117243741T>G
NM_000492.3:c.2813T>G

Protein change:

V938G

Links:

dbSNP: rs193922511

NCBI 1000 Genomes Browser:

rs193922511

Molecular consequence:

NM_000492.4:c.2813T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001169235	CFTR-France	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017))	Pathogenic (Jan 18, 2021)	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV005348085	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Aug 31, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001169235

CFTR-France

criteria provided, single submitter

(Claustres M et al. (Hum Mutat 2017))

Pathogenic
(Jan 18, 2021)

germline

curation

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

SCV005348085

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Aug 31, 2024)

germline

clinical testing

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants.

Claustres M, Thèze C, des Georges M, Baux D, Girodon E, Bienvenu T, Audrezet MP, Dugueperoux I, Férec C, Lalau G, Pagin A, Kitzis A, Thoreau V, Gaston V, Bieth E, Malinge MC, Reboul MP, Fergelot P, Lemonnier L, Mekki C, Fanen P, Bergougnoux A, et al.

Hum Mutat. 2017 Oct;38(10):1297-1315. doi: 10.1002/humu.23276. Epub 2017 Jun 28.

PubMed [citation]

PMID:: 28603918

Details of each submission

From CFTR-France, SCV001169235.2

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

#	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

From PreventionGenetics, part of Exact Sciences, SCV005348085.1

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

Description

The CFTR c.2813T>G variant is predicted to result in the amino acid substitution p.Val938Gly. This variant was reported in multiple individuals with congenital absence of vas deferens (CAVD) (Doerk et al 1997. PubMed ID: 9272157; Ratbi et al. 2007. PubMed ID: 17329263). It has also been reported along with a second pathogenic CFTR variant in a study of male patients with fertility problems (Rudnik-Schöneborn et al. 2021. PubMed ID: 33374015), an individual with idiopathic chronic pancreatitis (Sofia et al. 2016. PubMed ID: 27264265), an individual with abnormal newborn screening results for cystic fibrosis (Bozdogan et al. 2021. PubMed ID: 33572515), and along with the p.Phe508del variant in an individual with pancreatic sufficient cystic fibrosis (De Wachter et al 2017. PubMed ID: 28830496). Alternate substitutions of the same amino acid (p.Val938Leu) have been reported in individuals with CAVD (Luo et al. 2020. PubMed ID: 32777524; Table S1, Fang et al. 2022. PubMed ID: 36437957). An experimental study suggests the p.Vla938Gly substitution impacts protein function (Table S1, Bihler et al. 2024. PubMed ID: 38388235). This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Taken together, 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: Oct 13, 2024

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