ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.489+1G>T (rs78756941)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
American College of Medical Genetics and Genomics (ACMG) RCV000043565 SCV000071409 pathogenic Cystic fibrosis 2004-03-03 practice guideline curation Converted during submission to Pathogenic.
CFTR2 RCV000043565 SCV000071461 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000043565 SCV000485154 pathogenic Cystic fibrosis 2015-11-27 criteria provided, single submitter clinical testing
Courtagen Diagnostics Laboratory,Courtagen Life Sciences RCV000043565 SCV000236526 pathogenic Cystic fibrosis 2014-10-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000657900 SCV000331547 pathogenic not provided 2015-07-16 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763152 SCV000893739 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000657900 SCV000779664 pathogenic not provided 2018-05-07 criteria provided, single submitter clinical testing The c.489+1G>T (also reported as 621+1G>T) splice site variant is a well-described pathogenic variant reported in association with cystic fibrosis and other CFTR-related disorders (for examples see Zielenski et al., 1991; Amato et al., 2012, Wilschanski et al., 2006). This pathogenic variant destroys the canonical splice donor site in intron 4 results in abnormal gene splicing (Castellani et al., 2008). We interpret c.489+1G>T as a pathogenic variant.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000043565 SCV000584077 pathogenic Cystic fibrosis 2016-05-12 criteria provided, single submitter research
Invitae RCV000043565 SCV000075172 pathogenic Cystic fibrosis 2018-12-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs78756941, ExAC 0.01%). This splicing variant is clearly defined as a cystic fibrosis (CF) causative allele (PMID: 23974870) and is included in the American College of Medical Genetics (ACMG) panel of CF variants (PMID: 15371902). This variant is also known as 621+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 38799). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000043565 SCV000886212 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing

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