Submissions for variant NM_000492.4(CFTR):c.2128A>T (p.Lys710Ter)

dbSNP: rs75115087

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000007624	SCV000071541	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759034	SCV000888076	pathogenic	not provided	2018-04-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001004470	SCV001163515	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
CFTR-France	RCV000007624	SCV001169541	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000007624	SCV001194199	pathogenic	Cystic fibrosis	2019-12-04	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.2128A>T(K710*) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of the disease. Sources cited for classification include the following: PMID 23974870, 1379210 and 18456578. Classification of NM_000492.3(CFTR):c.2128A>T(K710*) 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	RCV000007624	SCV001587434	pathogenic	Cystic fibrosis	2022-07-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 7203). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 1379210, 10612827, 21520337, 23974870, 27086061). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys710*) 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000007624	SCV002103509	pathogenic	Cystic fibrosis	2022-02-11	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.2128A>T (p.Lys710X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250858 control chromosomes. c.2128A>T has been reported in the literature in multiple individuals affected with Cystic Fibrosis (examples: des Georges_2004, Fanen_1992, Alonso_2007). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Ambry Genetics	RCV000007624	SCV002729970	pathogenic	Cystic fibrosis	2022-06-18	criteria provided, single submitter	clinical testing	The p.K710* pathogenic mutation (also known as c.2128A>T), located in coding exon 14 of the CFTR gene, results from an A to T substitution at nucleotide position 2128. This changes the amino acid from a lysine to a stop codon within coding exon 14. 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.
Revvity Omics, Revvity	RCV000759034	SCV003823179	pathogenic	not provided	2022-08-25	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003473043	SCV004213404	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-09-04	criteria provided, single submitter	clinical testing
OMIM	RCV000007624	SCV000027825	pathogenic	Cystic fibrosis	1993-01-01	no assertion criteria provided	literature only
Natera, Inc.	RCV001826446	SCV002080711	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing