ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3854C>T (p.Ala1285Val) (rs397508617)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000585919 SCV000696994 uncertain significance not specified 2021-04-05 criteria provided, single submitter clinical testing Variant summary: CFTR c.3854C>T (p.Ala1285Val) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) 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 0.00066 in 250862 control chromosomes, predominantly at a frequency of 0.0053 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. This frequency is somewhat lower than the maximum expected for a pathogenic variant in CFTR causing Congenital Bilateral Absence of the Vas Deferens (CBAVD) (0.013), allowing no conclusion about variant significance. c.3854C>T has been reported in the literature in an Asian Indian individual affected with CBAVD (Sachdeva 2011). The variant was also found during carrier screening in homozygosity in an Asian Indian (Schwartz 2009) and an Australian individual (Archibald 2017), however the phenotype was not specified in these cases. These reports do not provide unequivocal conclusions about association of the variant with CBAVD. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Another 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001507714 SCV001713438 uncertain significance not provided 2021-01-29 criteria provided, single submitter clinical testing
Invitae RCV000577447 SCV001721256 benign Cystic fibrosis 2020-12-07 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577447 SCV000679387 not provided Cystic fibrosis no assertion provided literature only
Natera, Inc. RCV000577447 SCV001460116 uncertain significance Cystic fibrosis 2017-05-09 no assertion criteria provided clinical testing

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