NM_000492.4(CFTR):c.296C>T (p.Pro99Leu) AND Cystic fibrosis

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 8, 2017
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000577122.9

Allele description [Variation Report for NM_000492.4(CFTR):c.296C>T (p.Pro99Leu)]

NM_000492.4(CFTR):c.296C>T (p.Pro99Leu)

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.296C>T (p.Pro99Leu)

HGVS:

NC_000007.14:g.117530921C>T
NG_016465.4:g.70138C>T
NM_000492.4:c.296C>TMANE SELECT
NP_000483.3:p.Pro99Leu
NP_000483.3:p.Pro99Leu
LRG_663t1:c.296C>T
LRG_663:g.70138C>T
LRG_663p1:p.Pro99Leu
NC_000007.13:g.117170975C>T
NM_000492.3:c.296C>T

Protein change:

P99L

Links:

dbSNP: rs397508467

NCBI 1000 Genomes Browser:

rs397508467

Molecular consequence:

NM_000492.4:c.296C>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
SCV000679420	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no classification provided	not provided	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 14872121, 8663008
SCV000924243	CFTR2	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013))	Pathogenic (Dec 8, 2017)	germline	research	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001576101	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 31, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11732487, 14872121, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000679420

ClinVar Staff, National Center for Biotechnology Information (NCBI)

no classification provided

not provided

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000924243

CFTR2

reviewed by expert panel

(Sosnay PR et al. (Nat Genet 2013))

Pathogenic
(Dec 8, 2017)

germline

research

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

Citation Link,

SCV001576101

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 31, 2020)

germline

clinical testing

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

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	research, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Contribution of proline residues in the membrane-spanning domains of cystic fibrosis transmembrane conductance regulator to chloride channel function.

Sheppard DN, Travis SM, Ishihara H, Welsh MJ.

J Biol Chem. 1996 Jun 21;271(25):14995-5001.

PubMed [citation]

PMID:: 8663008

Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.

Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, Ramalho AS, Amaral MD, Dorfman R, Zielenski J, Masica DL, Karchin R, Millen L, Thomas PJ, Patrinos GP, Corey M, Lewis MH, Rommens JM, Castellani C, Penland CM, Cutting GR.

Nat Genet. 2013 Oct;45(10):1160-7. doi: 10.1038/ng.2745. Epub 2013 Aug 25.

PubMed [citation]

PMID:: 23974870
PMCID:: PMC3874936

See all PubMed Citations (5)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000679420.1

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

#	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 CFTR2, SCV000924243.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	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 Invitae, SCV001576101.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has been observed in individual(s) with cystic fibrosis (PMID: 11732487, 14872121). ClinVar contains an entry for this variant (Variation ID: 53610). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been reported to affect CFTR protein function (PMID: 29805046, 866 3008). This variant is present in population databases (rs397508467, ExAC 0.003%). This sequence change replaces proline with leucine at codon 99 of the CFTR protein (p.Pro99Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.

#	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: May 19, 2024

ClinVar

Relating variation to medicine