ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4225G>A (p.Glu1409Lys) (rs397508699)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000576918 SCV000886366 uncertain significance Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781273 SCV000919185 uncertain significance not specified 2019-04-12 criteria provided, single submitter clinical testing Variant summary: CFTR c.4225G>A (p.Glu1409Lys) results in a conservative amino acid change located in the ATPase domain (IPR003593) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250766 control chromosomes (gnomAD). c.4225G>A has been reported in the literature and in multiple databases in compound heterozygous individuals with varying clinical consequences, ranging from Congenital Bilateral Absence of the Vas Deferens (CBAVD) to Cystic Fibrosis with pancreatic insufficiency (Schrijver 2008, Girardet 2015, Mota 2018). These data indicate that the variant may be associated with disease. 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 VUS-possibly pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000576918 SCV000679147 not provided Cystic fibrosis no assertion provided literature only

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