ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3762A>T (p.Leu1254Phe)

gnomAD frequency: 0.00001  dbSNP: rs768411899
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001245313 SCV001418593 uncertain significance Cystic fibrosis 2021-08-13 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 1254 of the CFTR protein (p.Leu1254Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs768411899, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001283968 SCV001469499 uncertain significance not provided 2020-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001245313 SCV002027518 uncertain significance Cystic fibrosis 2021-09-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV001245313 SCV002623371 uncertain significance Cystic fibrosis 2021-08-11 criteria provided, single submitter clinical testing The p.L1254F variant (also known as c.3762A>T), located in coding exon 23 of the CFTR gene, results from an A to T substitution at nucleotide position 3762. The leucine at codon 1254 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001836235 SCV002075883 uncertain significance CFTR-related disorders 2018-12-26 no assertion criteria provided clinical testing

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