ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3222T>A (p.Phe1074Leu) (rs186045772)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000046829 SCV000220505 likely pathogenic Cystic fibrosis 2014-07-11 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000522824 SCV000861385 likely pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000522824 SCV000617533 pathogenic not provided 2017-07-13 criteria provided, single submitter clinical testing The F1074L pathogenic variant in the CFTR gene has been reported previously in cis with the 5T allele in siblings with a mild cystic fibrosis phenotype, but no other variant was found on the opposite CFTR allele (Casals et al., 1997). The F1074L variant has also been reported in cis with the 5T allele and phase unknown with the G551D variant in an individual with congenital bilateral absence of the vas deferens (Casals et al., 2000). Functional studies demonstrate that F1074L is associated with reduced chloride transport (Van Goor et al., 2014). The F1074L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F1074L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. The F1074L variant is reported in the CFTR2 database as being associated with varying consequences. Missense variants in nearby residues (G1069R, R1070Q, R1070W, L1077P) have been reported in the Human Gene Mutation Database in association with cystic fibrosis (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret F1074L as a pathogenic variant.
PharmGKB RCV000660789 SCV000783028 drug response ivacaftor response - Efficacy 2018-03-23 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.

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