ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3107C>A (p.Thr1036Asn) (rs397508498)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000577654 SCV000924217 pathogenic Cystic fibrosis 2019-03-11 reviewed by expert panel research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781270 SCV000919182 pathogenic not specified 2018-05-14 criteria provided, single submitter clinical testing Variant summary: CFTR c.3107C>A (p.Thr1036Asn) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-06 in 276656 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (7.2e-06 vs 0.013), allowing no conclusion about variant significance. The variant, c.3107C>A, has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Giusti_2007, McGinniss_2005, Salinas_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000781270 SCV001160337 likely pathogenic not specified 2019-02-21 criteria provided, single submitter clinical testing The CFTR c.3107C>A; p.Thr1036Asn variant (rs397508498) is reported in the literature in individuals affected with either pancreatic-sufficient or pancreatic-insufficient cystic fibrosis (CF) (Chavez-Saldana 2010, McGinniss 2005, Salinas 2016). This variant has been identified in affected individuals both in the homozygous state (McGinniss 2005) and in heterozygous individuals with an additional pathogenic variant (Salinas 2016). This variant is found on only two chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The threonine at codon 1036 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another variant at the same codon (p.Thr1036Ile) has been reported in individuals with CF and is considered pathogenic (Alibakhshi 2008, Sahami 2014). Based on available information, the p.Thr1036Asn variant is considered to be likely pathogenic. References: Alibakhshi R et al. Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations. J Cyst Fibros. 2008 Mar;7(2):102-9. Chavez-Saldana M et al. CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening. Rev Invest Clin. 2010 Nov-Dec;62(6):546-52. McGinniss MJ et al. Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. Hum Genet. 2005 Dec;118(3-4):331-8. Sahami A et al. Mutation Analysis of Exons 10 and 17a of CFTR Gene in Patients with Cystic Fibrosis in Kermanshah Province, Western Iran. J Reprod Infertil. 2014 Jan;15(1):49-56. Salinas DB 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 May 23;11(5):e0155624.
Baylor Genetics RCV001004291 SCV001163167 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577654 SCV000679029 not provided Cystic fibrosis no assertion provided literature only

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