ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.581G>T (p.Gly194Val) (rs397508763)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000729929 SCV000857631 uncertain significance not provided 2017-11-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002323 SCV001160217 likely pathogenic not specified 2019-01-08 criteria provided, single submitter clinical testing The c.581G>T; p.Gly194Val variant (rs397508763) has been reported in an individual with congenital bilateral absence of vas deferens in trans with a pathogenic variant (c.2657+5G>A) (Steiner 2011) and in an individual with elevated sweat chloride level that also carried a pathogenic p.Phe508del variant (Rychkova 2017). The p.Gly194Val variant is found on a single chromosome in the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at residue 194 is moderately conserved, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice site. Based on available information, this variant is considered to be likely pathogenic. References: Rychkova A et al. Developing gene-specific meta-predictor of variant pathogenicity. bioRxiv. 2017 Mar 10; doi: https://doi.org/10.1101/115956. Steiner B et al. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Hum Mutat. 2011 Aug;32(8):912-20.
CFTR-France RCV001009497 SCV001169592 pathogenic CFTR-related disorders 2018-01-29 criteria provided, single submitter curation
Ambry Genetics RCV001024572 SCV001186604 uncertain significance Inborn genetic diseases 2019-12-05 criteria provided, single submitter clinical testing The p.G194V variant (also known as c.581G>T), located in coding exon 6 of the CFTR gene, results from a G to T substitution at nucleotide position 581. The glycine at codon 194 is replaced by valine, an amino acid with dissimilar properties. This variant was described in two individuals with congenital bilateral absence of vas deferens in conjunction with a second CFTR varaint, who also had an intronic alteration in CFTR (Steiner B et al. Hum. Mutat., 2011 Aug;32:912-20; Akinsal EC et al. Andrologia, 2018 Feb;doi: 10.1111/and.12994). The p.G194V variant has been reported as a variant of varying clinical consequences (VVCC) (Sosnay PR et al. Pediatr. Clin. North Am., 2016 08;63:585-98; The Clinical and Functional TRanslation of CFTR (CFTR2); available at http://cftr2.org. Accessed January 15, 2020). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Johns Hopkins Genomics, Johns Hopkins University RCV001250516 SCV001425309 pathogenic Cystic fibrosis 2020-03-09 criteria provided, single submitter clinical testing CFTR variant associated with varying clinical consequence. See www.CFTR2.org for phenotype information.
Mayo Clinic Laboratories, Mayo Clinic RCV000729929 SCV001715944 uncertain significance not provided 2020-02-28 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001250516 SCV001822012 likely pathogenic Cystic fibrosis 2021-07-22 criteria provided, single submitter clinical testing

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