ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2780T>C (p.Leu927Pro)

dbSNP: rs397508435
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000056371 SCV000071510 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000056371 SCV000487119 likely pathogenic Cystic fibrosis 2016-10-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000056371 SCV000696924 pathogenic Cystic fibrosis 2017-06-13 criteria provided, single submitter clinical testing Variant summary: The CFTR c.2780T>C (p.Leu927Pro) variant involves the alteration of a highly conserved nucleotide and 5/5 in silico tools predict a damaging outcome. The deleterious effect of this change has been confirmed by functional studies where L927P was shown to have a reduce maturation level and severely affected Cl- transport. The variant is absent from the control population datasets of ExAC and gnomAD (~121324 and 216186 chrs tested) but was identified in multiple CF patients in compound heterozygosity with known pathogenic mutations. Multiple published reports and clinical diagnostic laboratories/reputable databases classified this variant as severe mutation/Pathogenic. Taking together, the variant has been classified as Pathogenic.
CFTR-France RCV000056371 SCV001169513 pathogenic Cystic fibrosis 2015-07-03 criteria provided, single submitter curation
Ambry Genetics RCV000056371 SCV002746349 pathogenic Cystic fibrosis 2022-07-08 criteria provided, single submitter clinical testing The p.L927P pathogenic mutation (also known as c.2780T>C), located in coding exon 17 of the CFTR gene, results from a T to C substitution at nucleotide position 2780. The leucine at codon 927 is replaced by proline, an amino acid with similar properties. This variant has been reported in multiple individuals with an elevated sweat chloride level in The Clinical and Functional TRanslation of CFTR (CFTR2) database (available at http://cftr2.org. Accessed 07/08/2022). This variant has also been reported in conjunction with other CFTR pathogenic mutations in multiple individuals with cystic fibrosis (Hermans CJ et al. Hum Mol Genet, 1994 Jul;3:1199-200; Storm K et al. J Cyst Fibros, 2007 Nov;6:371-5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Natera, Inc. RCV001826648 SCV002083543 pathogenic CFTR-related disorder 2017-03-17 no assertion criteria provided clinical testing

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