ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1519A>T (p.Ile507Phe) (rs1801178)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630461 SCV000751417 likely pathogenic Cystic fibrosis 2017-12-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with phenylalanine at codon 507 of the CFTR protein (p.Ile507Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed together with a pathogenic CFTR variant in an individual affected with Cystic Fibrosis (CF) (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). An in-frame deletion of this codon (p.Ile507del) has been clearly defined as a cystic fibrosis causative allele (PMID: 23974870). This suggests that the isoleucine residue is critical for CFTR protein function and that other variants at this position may also be pathogenic. 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.

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