ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.350G>T (p.Arg117Leu) (rs78655421)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000577295 SCV000800064 uncertain significance Cystic fibrosis 2018-05-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985692 SCV001134140 uncertain significance not provided 2019-06-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000577295 SCV001363742 likely pathogenic Cystic fibrosis 2019-06-11 criteria provided, single submitter clinical testing Variant summary: CFTR c.350G>T (p.Arg117Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250954 control chromosomes. c.350G>T has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Ferec_1995, Wallace_2003, D'Apice_2004). Several investigators have also reported that this variant is part of a complex allele with CFTR c.2991G>C (p.Leu997Phe) in patients with cystic fibrosis (Lucarelli_2010, Lucarelli_2015, Terlizzi_2016). The c.2991G>C variant, however, is found at a much higher frequency in controls (approximately 0.0022 in the gnomAD database). At least one publication reports experimental evidence suggesting that this variant impacts choride channel function (Hammerle_2001). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. In addition, a reputable database (CFTR2) stated that patients with this variant and another CFTR pathogenic variant have variable consequences. In one internally tested unaffected patient, this variant was found in homozgyous state, suggesting R117L in isolation may not be associated with disease and other modifier may contribute to pathogenicity. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000577295 SCV001433650 pathogenic Cystic fibrosis 2019-12-08 criteria provided, single submitter clinical testing CFTR variant associated with variable clinical consequences. See www.CFTR2.org for phenotype information.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577295 SCV000679441 not provided Cystic fibrosis no assertion provided literature only

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