Description
The R31C variant in the CFTR gene was first identified in the homozygous state in an asymptomatic individual and reported as a benign polymorphism (Ghanem et al., 1994). Other publications have reported this variant in association with disseminated bronchiectasis (Girodon et al., 1997), idiopathic pancreatitis (Gomez Lira et al., 2001), and oligospermia (Gallati et al., 2009), though a second CFTR variant was not identified in these cases. The R31C variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R31C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R31L) was identified in an adult woman with pulmonary symptoms but normal pulmonary function, normal pancreatic function, and repeated abnormal sweat chloride levels (mean value 90.9 mmol/L); no second CFTR variant was identified (Zielenski et al., 1995). Functional studies performed show that R31C affects protein biogenesis, although the defect is not complete (Jurkuvenaite et al., 2006). While the R31C variant has been deemed not to be cystic fibrosis-causing (Sosnay et al., 2013), it is possible this variant may have reduced penetrance in association with CF-related disorders. We interpret R31C as a variant of unknown significance.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
