ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.349C>G (p.Arg117Gly) (rs77834169)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506019 SCV000601103 uncertain significance not specified 2016-11-18 criteria provided, single submitter clinical testing
Counsyl RCV000670642 SCV000795520 uncertain significance Cystic fibrosis 2017-11-08 criteria provided, single submitter clinical testing
Johns Hopkins Genomics,Johns Hopkins University RCV000670642 SCV001167227 likely pathogenic Cystic fibrosis 2019-08-17 criteria provided, single submitter clinical testing Previously reported disease-causing CFTR variant associated with varying clinical consequences. See www.CFTR2.org for phenotype information.
Integrated Genetics/Laboratory Corporation of America RCV000506019 SCV001363740 uncertain significance not specified 2019-03-08 criteria provided, single submitter clinical testing Variant summary: The variant, CFTR c.349C>G (p.Arg117Gly) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.2e-05 in 276672 control chromosomes (gnomAD) and has been reported in the literature in individuals affected with congenital bilateral absence of the vas deferens (CBAVD) and idiopathic chronic pancreatitis (Daudin_2000 , Masson_2013). However, these reports do not provide unequivocal conclusions about association of the variant with Non-classic Cystic Fibrosis. At least one publication reports experimental evidence evaluating an impact on protein function. In this study the variant effect resulted in approximately 35% of normal activity (Raraigh_2018). Moreover, Lucarelli et al (Lucarelli_2010) state that the mutation in R117 residue is likely to cause CFTR-related disorders than CF itself. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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