Submissions for variant NM_000492.4(CFTR):c.310del (p.Arg104fs)

dbSNP: rs397508499

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046784	SCV000245978	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284615	SCV001470494	pathogenic	not provided	2019-09-18	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046784	SCV005205471	pathogenic	Cystic fibrosis	2024-06-25	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.310delA (p.Arg104GlufsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251148 control chromosomes (gnomAD). c.310delA has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Zielenski_1995). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 7537150). ClinVar contains an entry for this variant (Variation ID: 53653). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005031505	SCV005666791	pathogenic	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2024-04-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000046784	SCV005879321	pathogenic	Cystic fibrosis	2024-08-09	criteria provided, single submitter	clinical testing	The CFTR c.310del; p.Arg104GlufsTer3 variant (rs397508499, ClinVar Variation ID: 53653), also known as 441delA in legacy nomenclature, is reported in the literature in multiple individuals affected with cystic fibrosis (CFTR2 database, Zielenski 1995). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to CFTR2 database: https://cftr2.org/ Zielenski J et al. Identification of six mutations (R31L, 441delA, 681delC, 1461ins4, W1089R, E1104X) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Hum Mutat. 1995;5(1):43-7. PMID: 7537150.
Natera, Inc.	RCV001835663	SCV002080117	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing