NM_000492.4(CFTR):c.4202A>G (p.Glu1401Gly) AND Cystic fibrosis

Germline classification:: Uncertain significance (5 submissions)
Last evaluated:: Sep 5, 2021
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:: RCV000577394.12

Allele description [Variation Report for NM_000492.4(CFTR):c.4202A>G (p.Glu1401Gly)]

NM_000492.4(CFTR):c.4202A>G (p.Glu1401Gly)

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.4202A>G (p.Glu1401Gly)

HGVS:

NC_000007.14:g.117665524A>G
NG_016465.4:g.204741A>G
NM_000492.4:c.4202A>GMANE SELECT
NP_000483.3:p.Glu1401Gly
NP_000483.3:p.Glu1401Gly
LRG_663t1:c.4202A>G
LRG_663:g.204741A>G
LRG_663p1:p.Glu1401Gly
NC_000007.13:g.117305578A>G
NM_000492.3:c.4202A>G
NM_000492.4:c.4202A>G

Protein change:

E1401G

Links:

dbSNP: rs397508697

NCBI 1000 Genomes Browser:

rs397508697

Molecular consequence:

NM_000492.4:c.4202A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cystic fibrosis (CF)
Synonyms:: Mucoviscidosis
Identifiers:: MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

Recent activity

Clear Turn Off Turn On

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
SCV000679464	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000792618	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jul 5, 2017)	unknown	clinical testing	Citation Link,
SCV001183734	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (May 22, 2019)	germline	clinical testing	Citation Link,
SCV002027541	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003522356	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26277102, 28492532

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	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Do common in silico tools predict the clinical consequences of amino-acid substitutions in the CFTR gene?

Dorfman R, Nalpathamkalam T, Taylor C, Gonska T, Keenan K, Yuan XW, Corey M, Tsui LC, Zielenski J, Durie P.

Clin Genet. 2010 May;77(5):464-73. doi: 10.1111/j.1399-0004.2009.01351.x. Epub 2009 Jan 6.

PubMed [citation]

PMID:: 20059485

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

See all PubMed Citations (4)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000679464.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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 Counsyl, SCV000792618.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV001183734.3

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

Description

The p.E1401G variant (also known as c.4202A>G), located in coding exon 26 of the CFTR gene, results from an A to G substitution at nucleotide position 4202. The glutamic acid at codon 1401 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

From Genome-Nilou Lab, SCV002027541.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003522356.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glutamic acid with glycine at codon 1401 of the CFTR protein (p.Glu1401Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with congenital absence of vas deferens (CAVD) (PMID: 26277102). ClinVar contains an entry for this variant (Variation ID: 53921). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Apr 15, 2024

ClinVar

Relating variation to medicine