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NM_000492.4(CFTR):c.2846A>T (p.His949Leu)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Feb 9, 2021)
Last evaluated:
Jan 8, 2021
Accession:
VCV000053578.4
Variation ID:
53578
Description:
single nucleotide variant
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NM_000492.4(CFTR):c.2846A>T (p.His949Leu)

Allele ID
68246
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q31.2
Genomic location
7: 117603720 (GRCh38) GRCh38 UCSC
7: 117243774 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.14:g.117603720A>T
NG_016465.4:g.142937A>T
NM_000492.4:c.2846A>T MANE Select NP_000483.3:p.His949Leu missense
... more HGVS
Protein change
H949L
Other names
-
Canonical SPDI
NC_000007.14:117603719:A:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00010
Links
ClinGen: CA326942
dbSNP: rs397508444
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Jan 8, 2021 RCV001290523.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations May 8, 2020 RCV000577071.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CFTR - - GRCh38
GRCh37
1974 2730

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Cystic fibrosis
Allele origin: unknown
Mendelics
Accession: SCV001137488.1
Submitted: (Oct 22, 2019)
Evidence details
Uncertain significance
(May 08, 2020)
criteria provided, single submitter
Method: clinical testing
Cystic fibrosis
Allele origin: germline
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001425365.1
Submitted: (May 28, 2020)
Evidence details
Publications
PubMed (2)
Comment:
CFTR c.2846A>T has been identified an individual with an equivocal sweat chloride concentration. There is an entry in ClinVar for this variant and it (rs397508444) … (more)
Uncertain significance
(Jan 08, 2021)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001478575.1
Submitted: (Feb 09, 2021)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: CFTR c.2846A>T (p.His949Leu) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded … (more)
not provided
(-)
no assertion provided
Method: literature only
CFTR-related disorders
Allele origin: germline
ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000679010.1
Submitted: (Mar 30, 2013)
Evidence details
Publications
PubMed (1)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Genotype-phenotype correlation in cystic fibrosis patients bearing [H939R;H949L] allele. Polizzi A Genetics and molecular biology 2011 PMID: 21931512
Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. McGinniss MJ Human genetics 2005 PMID: 16189704

Text-mined citations for rs397508444...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021