ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2981T>G (p.Phe994Cys) (rs397508469)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000855590 SCV000696940 uncertain significance not specified 2019-03-29 criteria provided, single submitter clinical testing Variant summary: CFTR c.2981T>G (p.Phe994Cys) results in a non-conservative amino acid change located in the 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 4.1e-06 in 245896 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant of interest has been reported in the literature and in multiple databases in a male patient affected with Congenital Bilateral Absence of the Vas Deferens (CBAVD) who carried a severe disease variant (likely deltaF508) on the other allele (Dorfman 2010, Claustres 2017); however this patient also carried a mild pathogenic variant (TG12T5) in cis, which could explain his phenotype. These reports therefore do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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. Based on the evidence outlined above, the variant was classified as uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000586753 SCV000862907 uncertain significance not provided 2018-08-09 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577330 SCV000679421 not provided Cystic fibrosis no assertion provided literature only

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