ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1393-1G>A (rs397508200)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000056347 SCV000071451 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000056347 SCV000205857 pathogenic Cystic fibrosis 2013-10-18 criteria provided, single submitter clinical testing The 1393-1G>A variant in CFTR causes cystic fibrosis when combined with another CF-causing variant. It has been previously identified in 2 homozygous and 3 comp ound heterozygous individuals with cystic fibrosis and was found to segregate wi th disease in 1 family member (Dork 1993, Ramalho 2003, Wahab 2004, Ashavaid 200 5, Nikolic 2013). It has not been identified in large population studies. This v ariant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent pro tein (Ramalho 2003). In summary, this variant meets our criteria to be classifie d as pathogenic (http://pcpgm.partners.org/LMM) based upon segregation studies, absence from controls, and functional evidence.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506225 SCV000601043 pathogenic not provided 2017-04-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506518 SCV000603063 pathogenic not specified 2017-03-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000056347 SCV000696839 pathogenic Cystic fibrosis 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The c.1393-1G>A in CFTR gene is a splice-site variant that alters a highly conserved nucleotide. 5/5 in silico tools via Alamut predict this variant to disrupt a canonical splicing acceptor sequence, although these predictions are yet to be confirmed by the functional studies. The variant is present in control dataset of ExAC at a low frequency of 0.000049 (6/121108 chrs tested) which does not exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.0129). This variant appears to be very common in Palestina (Siryani, 2015). The variant was found homozygously or in compound heterozygosity in multiple affected individuals with established dx of CF. Patients, homozygous for the variant of interest, presented with elevated sweat Cl- (ranging from 110 to 148 mmol/L) and PI. Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic.
Baylor Genetics RCV001004449 SCV001163494 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000056347 SCV001169562 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation

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