Submissions for variant NM_000492.4(CFTR):c.224G>A (p.Arg75Gln)

dbSNP: rs1800076

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000116686	SCV000110853	likely benign	not specified	2017-08-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000116686	SCV000150650	likely benign	not specified	2016-06-03	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000116686	SCV000204215	benign	not specified	2014-02-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000116686	SCV000304479	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001095213	SCV000466502	likely benign	CFTR-related disorder	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000029494	SCV000562313	benign	Cystic fibrosis	2024-02-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000513754	SCV000601071	uncertain significance	not provided	2023-07-06	criteria provided, single submitter	clinical testing	The CFTR c.224G>A (p.Arg75Gln) variant has been reported in the published literature in individuals affected with pancreatitis (PMID: 25033378 (2014), 27555793 (2016), 32447501 (2021), 35096544 (2022)), chronic obstructive pulmonary disease (PMID: 15463907 (2004), 34996830 (2022)), rheumatoid arthritis and/or diffuse bronchiectasis (PMID: 21131649 (2011), 25797027 (2015)), and idiopathic infertility (PMID: 32155011 (2020)). Functional studies show the variant as having acceptable (PMID: 18306312 (2008), 25033378 (2014)) or reduced chloride conductance activity (PMID: 23974870 (2013), 35418593 (2022)), reduced mRNA expression and processing (PMID: 25797027 (2015)), and defects in bicarbonate conductance (PMID: 25033378 (2014)). However, other studies report the variant CFTR protein is processed and glycosylated in a manner comparable to the wild-type (PMID: 18306312 (2008), 23974870 (2013), 25033378 (2014), 35418593 (2022)). The frequency of this variant in the general population, 0.039 (1980/50646 chromosomes in North-Western European subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000513754	SCV000602979	likely benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000513754	SCV000609754	uncertain significance	not provided	2017-09-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513754	SCV001155236	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	CFTR: BS1, BS2
CFTR-France	RCV000029494	SCV001169171	benign	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation	the variant does not result in CFTR-RD neither
Ambry Genetics	RCV000029494	SCV001175697	benign	Cystic fibrosis	2014-12-01	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab	RCV000029494	SCV001653444	uncertain significance	Cystic fibrosis	2021-05-18	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000029494	SCV002507371	benign	Cystic fibrosis	2022-02-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000119039	SCV002529690	likely benign	Hereditary pancreatitis	2021-05-18	criteria provided, single submitter	curation
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000513754	SCV005196602	likely benign	not provided	2023-10-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029494	SCV000052145	benign	Cystic fibrosis	2014-02-22	no assertion criteria provided	clinical testing
GeneReviews	RCV000119039	SCV000153745	not provided	Hereditary pancreatitis		no assertion provided	literature only
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000582582	SCV000692319	uncertain significance	Lung disease, non-specific	2015-05-14	no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV001249413	SCV001423414	not provided	Abnormality of the pancreas		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 02-10-2019 by Lab or GTR ID 500068. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc.	RCV000029494	SCV001453945	benign	Cystic fibrosis	2019-08-06	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001095213	SCV002507458	uncertain significance	CFTR-related disorder	2022-02-01	no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000029494	SCV004171577	uncertain significance	Cystic fibrosis	2023-11-24	no assertion criteria provided	clinical testing