NM_000492.4(CFTR):c.2687C>T (p.Thr896Ile) AND Cystic fibrosis

Germline classification:: Uncertain significance (5 submissions)
Last evaluated:: Mar 1, 2023
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:: RCV000671200.10

Allele description [Variation Report for NM_000492.4(CFTR):c.2687C>T (p.Thr896Ile)]

NM_000492.4(CFTR):c.2687C>T (p.Thr896Ile)

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.2687C>T (p.Thr896Ile)

HGVS:

NC_000007.14:g.117603561C>T
NG_016465.4:g.142778C>T
NM_000492.4:c.2687C>TMANE SELECT
NP_000483.3:p.Thr896Ile
NP_000483.3:p.Thr896Ile
LRG_663t1:c.2687C>T
LRG_663:g.142778C>T
LRG_663p1:p.Thr896Ile
NC_000007.13:g.117243615C>T
NM_000492.3:c.2687C>T
NM_000492.4:c.2687C>T

Protein change:

T896I

Links:

dbSNP: rs752617117

NCBI 1000 Genomes Browser:

rs752617117

Molecular consequence:

NM_000492.4:c.2687C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000796152	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Dec 4, 2017)	unknown	clinical testing	Citation Link,
SCV001137485	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002027465	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]
SCV002255418	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10571949, 11354633, 22664493, 28492532
SCV002739106	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 1, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10571949, 11354633 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

Association of CFTR gene mutation with bronchial asthma.

Maurya N, Awasthi S, Dixit P.

Indian J Med Res. 2012 Apr;135(4):469-78. Review.

PubMed [citation]

PMID:: 22664493
PMCID:: PMC3385229

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000796152.1

#	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 Mendelics, SCV001137485.1

#	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 Genome-Nilou Lab, SCV002027465.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002255418.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 896 of the CFTR protein (p.Thr896Ile). This variant is present in population databases (rs752617117, gnomAD 0.006%). This missense change has been observed in individual(s) with asthma or bronchiectasis (PMID: 10571949, 11354633, 22664493). ClinVar contains an entry for this variant (Variation ID: 555384). 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

From Ambry Genetics, SCV002739106.3

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

Description

The p.T896I variant (also known as c.2687C>T), located in coding exon 17 of the CFTR gene, results from a C to T substitution at nucleotide position 2687. The threonine at codon 896 is replaced by isoleucine, an amino acid with similar properties. This variant was identified in an individual with asthma and an individual with disseminated bronchiectasis; a second CFTR alteration was not identified in either individual (Lázaro C et al. Hum. Mutat., 1999;14:510-9; Tzetis M et al. Hum. Genet., 2001 Mar;108:216-21). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine