ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1730A>T (p.Tyr577Phe) (rs397508286)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000577606 SCV000792633 uncertain significance Cystic fibrosis 2017-07-05 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000577606 SCV001430626 likely benign Cystic fibrosis 2020-08-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285536 SCV001471990 uncertain significance none provided 2019-12-23 criteria provided, single submitter clinical testing The CFTR c.1730A>T; p.Tyr577Phe variant (rs39750828) is reported in the literature on the same chromosome as the c.1742dupT variant in an individual affected with cystic fibrosis that also carried the common pathogenic p.Phe508del variant (Stuhrmann 1997). While p.Tyr577Phe has also been reported in an individual with infertility without the linked c.1742dupT variant, it is not clear that the detection methods used in this study would have detected both variants (Morea 2005). The p.Tyr577Phe variant is reported on a single chromosome (1/250312 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. The tyrosine at codon 577 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic acceptor splice site, although RNA analyses would be required to confirm this. Given the lack of clinical and functional data, the significance of the p.Tyr577Phe variant is uncertain at this time. References: Morea A et al. Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility. Mol Hum Reprod. 2005 Aug;11(8):607-14. Stuhrmann M et al. Detection of 100% of the CFTR mutations in 63 CF families from Tyrol. Clin Genet. 1997 Oct;52(4):240-6.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577606 SCV000678926 not provided Cystic fibrosis no assertion provided literature only

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