ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3457G>A (p.Val1153Met) (rs143120209)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000823843 SCV000964714 uncertain significance Cystic fibrosis 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1153 of the CFTR protein (p.Val1153Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CFTR-related disease. 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: "Benign"; 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000983 SCV001158085 uncertain significance not specified 2018-12-30 criteria provided, single submitter clinical testing The CFTR c.3457G>A; p.Val1153Met variant (rs143120209), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found on only three chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 1153 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another variant at this codon (p.Val1153Glu) has been reported in an individual with congenital bilateral absence of the vas deferens (Dork 1997) and exhibits decreased chloride channel function (Raraigh 2018). However, given the lack of clinical and functional data, the significance of the p.Val1153Met variant is uncertain at this time. References: Dork T et al. Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens. Hum Genet. 1997 Sep;100(3-4):365-77. Raraigh KS et al. Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity. Am J Hum Genet. 2018 Jun 7;102(6):1062-1077.

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