Submissions for variant NM_000492.4(CFTR):c.413T>C (p.Leu138Pro)

gnomAD frequency: 0.00001  dbSNP: rs1800078

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001052278	SCV001216480	uncertain significance	Cystic fibrosis	2022-05-08	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 138 of the CFTR protein (p.Leu138Pro). This variant is present in population databases (rs1800078, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 848508). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics	RCV001052278	SCV002629369	uncertain significance	Cystic fibrosis	2021-06-09	criteria provided, single submitter	clinical testing	The p.L138P variant (also known as c.413T>C), located in coding exon 4 of the CFTR gene, results from a T to C substitution at nucleotide position 413. The leucine at codon 138 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003478678	SCV004221698	uncertain significance	not provided	2023-08-03	criteria provided, single submitter	clinical testing	The CFTR c.413T>C (p.Leu138Pro) variant, to the best of our knowledge, has not been reported in the published literature. The frequency of this variant in the general population, 0.000011 (3/282144 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc.	RCV001832481	SCV002080136	uncertain significance	CFTR-related disorders	2018-09-27	no assertion criteria provided	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001832481	SCV002754563	uncertain significance	CFTR-related disorders	2022-02-23	no assertion criteria provided	clinical testing