Submissions for variant NM_000492.4(CFTR):c.1487G>A (p.Trp496Ter)

dbSNP: rs397508216

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000576357	SCV000677627	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Counsyl	RCV000576357	SCV000794189	pathogenic	Cystic fibrosis	2017-09-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576357	SCV002243477	pathogenic	Cystic fibrosis	2021-08-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with cystic fibrosis (PMID: 15176679, 7531541, 12752573). This variant is also known as c.1619G>A. ClinVar contains an entry for this variant (Variation ID: 53265). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp496*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922).
Ambry Genetics	RCV000576357	SCV003855920	pathogenic	Cystic fibrosis	2022-12-03	criteria provided, single submitter	clinical testing	The p.W496* pathogenic mutation (also known as c.1487G>A), located in coding exon 11 of the CFTR gene, results from a G to A substitution at nucleotide position 1487. This changes the amino acid from a tryptophan to a stop codon within coding exon 11. This alteration has been identified in individuals diagnosed with cystic fibrosis (Kanavakis E et al. Clin Genet, 2003 May;63:400-9; Decaestecker K et al. Eur Respir J, 2004 May;23:679-84). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000576357	SCV000679107	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV001826612	SCV002080603	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing