ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3485G>T (p.Arg1162Leu) (rs1800120)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000726998 SCV000883574 pathogenic not provided 2017-10-04 criteria provided, single submitter clinical testing The CFTR c.3485G>T, p.Arg1162Leu variant (rs1800120) has not been associated with classic cystic fibrosis (Fanen 1992, Narzi 2007, Salinas 2015, Sosnay 2013, CFTR2 database), but has been found in individuals with CFTR-related disorders, such as bronchiectasis and chronic pancreatitis (Casals 2004, Groman 2002, Lazaro 1999, Ziedalski 2006). The variant has also been identified in 15 individuals with CFTR-related disorders, including 5 individuals who carry another pathogenic variant. The p.Arg1162Leu variant is listed in ClinVar (Variation ID: 256253), and observed in the general population databases at a frequency of 0.08 percent in the 1000 Genomes Project (4/5008 alleles), 0.06 percent in the Exome Variant Server (8/13004 alleles, 1 homozygote), and 0.07 percent in the Genome Aggregation Database (187/276320 alleles). The variant is slightly enriched in pancreatitis patients tested ARUP Laboratories compared to the general population (Genome Aggregation Database), with an odds ratio of 2.2 (95 percent CI: 1.3 to 3.7, adjusted p-value: 0.04). The arginine at position 1162 is highly conserved (Alamut v2.9.0), and computational algorithms (Align GVGD, Mutation Taster, PolyPhen-2, SIFT) predict that the variant has an impact on CFTR protein structure or function. Although the CFTR p.Arg1162Leu variant is not expected to cause classical cystic fibrosis, when paired with a second pathogenic CFTR variant on the opposite chromosome, the p.Arg1162Leu variant may contribute to CFTR-related disorders, such as pancreatitis. References: CFTR database: http://cftr.org/ Casals T et al. Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis? Pancreas. 2004; 28(4):374-9. Fanen P et al. Molecular characterization of cystic fibrosis: 16 novel mutations identified by analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR) coding regions and splice site junctions. Genomics. 1992; 13(3):770-6. Groman J et al. Variant cystic fibrosis phenotypes in the absence of CFTR mutations. N Engl J Med. 2002; 347(6):401-7. Lazaro C et al. Missense mutations in the cystic fibrosis gene in adult patients with asthma. Hum Mutat. 1999; 14(6):510-9. Narzi L et al. Does cystic fibrosis neonatal screening detect atypical CF forms? Extended genetic characterization and 4-year clinical follow-up. Clin Genet. 2007; 72(1):39-46. Salinas D 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; 11(5):e0155624. Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013; 45(10):1160-7. Ziedalski T et al. Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection. Chest. 2006; 130(4):995-1002.
Counsyl RCV000462037 SCV000795466 likely benign Cystic fibrosis 2017-11-22 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726998 SCV000704812 uncertain significance not provided 2018-08-30 criteria provided, single submitter clinical testing
Invitae RCV000462037 SCV000562305 benign Cystic fibrosis 2017-12-27 criteria provided, single submitter clinical testing
PreventionGenetics RCV000248703 SCV000304490 likely benign not specified criteria provided, single submitter clinical testing

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