Submissions for variant NM_000492.4(CFTR):c.1211del

dbSNP: rs1235397597

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000576433	SCV000677590	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Mendelics	RCV000576433	SCV000886306	pathogenic	Cystic fibrosis	2018-11-05	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985673	SCV001134111	pathogenic	not provided	2018-12-24	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 symptomatic patient, and not found in general population data.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000985673	SCV001473548	pathogenic	not provided	2020-02-21	criteria provided, single submitter	clinical testing	The CFTR c.1211delG; p.Gly404fs variant (rs1235397597), also published as 1343delG, has been reported in the literature in one individual with CF and an additional pathogenic variant (Salinas 2016). The variant is reported as pathogenic in the ClinVar database (Variation ID: 487376) but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), 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. Considering available information, this variant is classified as pathogenic. REFERENCE Salinas DB et al. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California. PLoS One. 2016 May 23;11(5):e0155624.
Genome-Nilou Lab	RCV000576433	SCV001810342	pathogenic	Cystic fibrosis	2021-07-22	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000576433	SCV002570328	pathogenic	Cystic fibrosis	2022-09-06	criteria provided, single submitter	clinical testing	Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Ambry Genetics	RCV000576433	SCV002653748	pathogenic	Cystic fibrosis	2023-06-22	criteria provided, single submitter	clinical testing	The c.1211delG (also known as 1343delG) pathogenic mutation, located in coding exon 10 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 1211, causing a translational frameshift with a predicted alternate stop codon (p.G404Dfs*38). This mutation was identified in one pancreatic insufficient individual with elevated sweat chloride in conjunction with p.F508del; however, phase information was not provided (Salinas DB et al. PLoS One, 2016 May;11:e0155624). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000576433	SCV004039522	pathogenic	Cystic fibrosis	2023-08-15	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.1211delG (p.Gly404AspfsX38) 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 246876 control chromosomes. c.1211delG has been reported in the literature in individuals with pancreatic insufficiency (Salinas_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV003471912	SCV004213520	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-04-22	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000576433	SCV001456063	pathogenic	Cystic fibrosis	2020-09-16	no assertion criteria provided	clinical testing