ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1516A>G (p.Ile506Val) (rs1800091)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000007551 SCV000284995 benign Cystic fibrosis 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000245320 SCV000304472 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000245320 SCV000331550 benign not specified 2016-07-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000245320 SCV000601048 benign not specified 2016-12-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000245320 SCV000603019 uncertain significance not specified 2018-11-15 criteria provided, single submitter clinical testing The CFTR c.1516A>G; p.Ile506Val variant (rs1800091) is reported in the literature in at least two individuals with a severe pathogenic variant on the opposite allele and no symptoms of cystic fibrosis (Kobayashi 1990). However, another variant in the same codon, p.Ile506Leu, has been described in the literature in two individuals with a severe pathogenic variant on the opposite allele with symptoms of pancreatic sufficient cystic fibrosis (Standvick 2001). Additionally, other amino acid substitutions at this codon (Met, Ser, Thr) have been reported in individuals with cystic fibrosis (Castellani 2008, Chevalier-Porst 1994, Deufel 199). The p.Ile506Val variant is reported in ClinVar (Variation ID: 7131), and is found in the general population with an overall allele frequency of 0.036% (101/282,660 alleles) in the Genome Aggregation Database. The isoleucine at codon 506 highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to conflicting information, the clinical significance of the p.Ile506Val variant is uncertain at this time. References: Castellani C et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008 May;7(3):179-96. Chevalier-Porst F et al. Mutation analysis in 600 French cystic fibrosis patients. J Med Genet. 1994 Jul;31(7):541-4. Deufel A et al. Three novel mutations (I506S, S466X, 1651A-->T) in exon 10 of the cystic fibrosis transmembrane conductance regulator (CFTR) detected in patients of southern German descent. Hum Mutat. 1994;3(1):64-6. Kobayashi K et al. Benign missense variations in the cystic fibrosis gene. Am J Hum Genet. 1990 47(4):611-5. Strandvik B et al. Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: identification of 12 novel mutations. Genet Test. 2001 5(3):235-42.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759754 SCV000889286 benign not provided 2016-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011880 SCV001172259 benign Inborn genetic diseases 2015-02-12 criteria provided, single submitter clinical testing
OMIM RCV000007551 SCV000027752 benign Cystic fibrosis 1990-10-01 no assertion criteria provided literature only

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