ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.31G>A (p.Val11Ile) (rs1800072)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589079 SCV000696956 uncertain significance not provided 2017-02-21 criteria provided, single submitter clinical testing Variant summary: The CFTR c.31G>A (p.Val11Ile) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome for this variant. This variant was found in 19/120978 control chromosomes at a frequency of 0.0001571, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported in one patient with asthma who also carried p.M1R, in one patient with clinical features of CF, and in a chronic pancreatitis patient, all without strong evidence for causality. Due to the lack of sufficient clinical information and the absence of functional studies, the variant has currently been classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000630460 SCV000751416 uncertain significance Cystic fibrosis 2019-08-13 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 11 of the CFTR protein (p.Val11Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs1800072, ExAC 0.03%). This variant has been reported in an individual affected with chronic pancreatitis (PMID: 27171515), and an individual with clinical manifestations consistent with the spectrum of cystic fibrosis, but no second variant was described in this individual (PMID: 15858154). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002302 SCV001160188 uncertain significance not specified 2018-12-27 criteria provided, single submitter clinical testing The CFTR c.31G>A; p.Val11Ile variant (rs1800072), is reported in the literature in individuals affected with chronic pancreatitis or asthma (Maurya 2012, Palermo 2016, Tzetis 2001). This variant is reported as uncertain significance by multiple laboratories in ClinVar (Variation ID: 495928), and is found in the non-Finnish European population with an allele frequency of 0.031% (40/128,740 alleles) in the Genome Aggregation Database. The valine at codon 11 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Val11Ile variant is uncertain at this time. References: Maurya N et al. Association of CFTR gene mutation with bronchial asthma. Indian J Med Res. 2012 Apr;135(4):469-78. Palermo JJ et al. Genophenotypic Analysis of Pediatric Patients With Acute Recurrent and Chronic Pancreatitis. Pancreas. 2016 Oct;45(9):1347-52. Tzetis M et al. CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease. Hum Genet. 2001 108(3):216-21.
Ambry Genetics RCV001019151 SCV001180474 uncertain significance Inborn genetic diseases 2019-01-09 criteria provided, single submitter clinical testing Insufficient evidence

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