ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.346G>A (p.Glu116Lys) (rs397508571)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755922 SCV000883591 likely pathogenic not provided 2018-05-30 criteria provided, single submitter clinical testing The CFTR c.346G>A; p.Glu116Lys variant (rs397508571) has been described in the compound heterozygous state in individuals with mild cystic fibrosis and allergic bronchopulmonary aspergillosis, and in the homozygous state in one individual with a CFTR-related disorder with unknown clinical phenotype (see link to SickKids database, Burgel 2010, Schrijver 2005). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The glutamic acid at codon 116 is highly conserved, but computational algorithms (PolyPhen-2: probably damaging, SIFT: tolerated) are inconclusive on the effects of this variant on protein structure and/or function. Functional studies demonstrate destabilization of the open state of the chloride channel and slightly reduced transport of mature CFTR protein to the cell surface (Hammerle 2001). Based on available information, this variant is considered likely pathogenic. References: SickKids Databse: Burgel P et al. Non-classic cystic fibrosis associated with D1152H CFTR mutation. Clin Genet. 2010 Apr;77(4):355-64. Hammerle M et al. Disease-associated mutations in the extracytoplasmic loops of cystic fibrosis transmembrane conductance regulator do not impede biosynthetic processing but impair chloride channel stability. J Biol Chem. 2001 May 4;276(18):14848-54. Schrijver I et al. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. J Mol Diagn. 2005 May;7(2):289-99.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577691 SCV000679379 not provided Cystic fibrosis no assertion provided literature only

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