Submissions for variant NM_000492.4(CFTR):c.1155_1156dup (p.Asn386fs)

dbSNP: rs121908785

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046247	SCV000245887	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046247	SCV000696821	pathogenic	Cystic fibrosis	2016-11-17	criteria provided, single submitter	clinical testing	Variant summary: The CFTR c.1155_1156dupTA (p.Asn386Ilefs) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 3/118554 (1/39525), which does not exceed the estimated maximal expected allele frequency for a pathogenic CFTR variant 1/77. The variant of interest has been reported in multiple affected individuals, along with multiple clinical diagnostic laboratories/databases citing the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985671	SCV001134109	pathogenic	not provided	2019-04-13	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 found in general population data that is consistent with pathogenicity. Occurs in multiple cases with a recessive pathogenic variant in the same gene.
Baylor Genetics	RCV001004257	SCV001163133	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000046247	SCV001167213	pathogenic	Cystic fibrosis	2019-06-25	criteria provided, single submitter	clinical testing	Previously reported disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Myriad Genetics, Inc.	RCV000046247	SCV001193919	pathogenic	Cystic fibrosis	2019-12-07	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.1155_1156dupTA(N386Ifs*3, aka 1288insTA) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 15365999 and 16980811. Classification of NM_000492.3(CFTR):c.1155_1156dupTA(N386Ifs*3, aka 1288insTA) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000046247	SCV001585851	pathogenic	Cystic fibrosis	2024-06-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn386Ilefs*3) 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). This variant is present in population databases (rs779935991, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 15365999). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1153_1154dupTA. ClinVar contains an entry for this variant (Variation ID: 487393). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000046247	SCV002624705	pathogenic	Cystic fibrosis	2015-05-01	criteria provided, single submitter	clinical testing	The c.1155_1156dupTA pathogenic mutation (also known as 1288insTA), located in coding exon 9 of the CFTR gene, results from a duplication of TA at nucleotide position 1155, causing a translational frameshift with a predicted alternate stop codon (p.Asn386Ilefs*3). In one study, this mutation was described in five unrelated Hispanic patients with cystic fibrosis. This mutation was confirmed to be in trans with another pathogenic CFTR mutation in at least one patient and was homozygous in another patient whose parents were consanguineous (first cousins). All five patients had elevated sweat chloride levels and pancreatic insufficiency; other clinical features included failure to thrive and recurrent respiratory tract infections (Alper OM et al. Hum. Mutat. 2004 Oct; 24(4):353). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Baylor Genetics	RCV003471915	SCV004213351	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-09-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001829609	SCV002078198	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing