ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.948del (p.Phe316fs) (rs75528968)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007583 SCV000071464 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079016 SCV000331317 pathogenic not provided 2012-11-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000079016 SCV000601138 pathogenic not provided 2016-12-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000007583 SCV000697060 pathogenic Cystic fibrosis 2020-07-24 criteria provided, single submitter clinical testing Variant summary: CFTR c.948delT (p.Phe316LeufsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.4e-05 in 251272 control chromosomes (gnomAD). c.948delT has been reported in the literature, in the compound heterozygous or homozygous state, in multiple individuals affected with Cystic Fibrosis (e.g. Claustres_1992, McKone_2003, Claustres_2017, da Rosa_2018). These data indicate that the variant is very likely to be associated with disease. Seven ClinVar submitters including an expert panel (CFTR2) (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000079016 SCV000885173 pathogenic not provided 2017-11-30 criteria provided, single submitter clinical testing The CFTR c.948delT, p.Phe316fs variant (rs121908744), also known as 1078delT, has been reported in multiple individuals with the pancreatic insufficient form of cystic fibrosis (Claustres 1992, Ooi 2012, Sosnay 2013, CFTR2 database). It is listed as pathogenic in ClinVar (Variation ID: 7163), and not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). The variant introduces a frameshift, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the p.Phe316fs variant is classified as pathogenic. References: CFTR2 database: http://cftr2.org/ Claustres M et al. A new mutation (1078delT) in exon 7 of the CFTR gene in a southern French adult with cystic fibrosis. Genomics. 1992; 13(3):907-8. Ooi C. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012; 11(5):355-62. Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013; 45(10):1160-7.
Mendelics RCV000007583 SCV000886238 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
CFTR-France RCV000007583 SCV001169327 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Ambry Genetics RCV001019400 SCV001180753 pathogenic Inborn genetic diseases 2018-12-17 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Myriad Women's Health, Inc. RCV000007583 SCV001193960 pathogenic Cystic fibrosis 2019-12-04 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.948delT(aka 1078delT) is classified as pathogenic in the context of cystic fibrosis and is associated with classic disease. Sources cited for classification include the following: PMID 9259197, 1284538, 18456578, 23974870, 22658665, 24440181 and 1379211. Classification of NM_000492.3(CFTR):c.948delT(aka 1078delT) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000007583 SCV000027784 pathogenic Cystic fibrosis 1993-12-01 no assertion criteria provided literature only

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