Investigation of CFTR: c.۳۶۴T>A (p.Tyr۱۲۲Asn) variant using in silico predictive tools

As a disorder with autosomal recessive (AR) inheritance, cystic fibrosis (CF) is caused by pathogenic variantsin cystic fibrosis transmembrane conductance regulator (CFTR) gene. Therefore, it is necessary to classifythe variants identified in this gene into pathogenic and non-pathogenic types. The aim of this study was toinvestigate the deleterious effect of CFTR: c.۳۶۴T>A (p.Tyr۱۲۲Asn) variant. To this end, ten in silicopredictive tools were selected. Our results are shown in the table below; accordingly, CFTR: c.۳۶۴T>A(p.Tyr۱۲۲Asn) variant had deleterious effects on all in silico tools used by us. This variant was first reportedby Iranome project (http://www.iranome.ir/) in a healthy individual with Lurish (Luri) ethnicity from Iran (inheterozygous form). Our search in the databases of LOVD, HGMD, dbSNP, ClinVar, gnomAD, ۱KGP,CFTR۱, and CFTR۲ as well as in the google scholar did not reveal any other reports for CFTR: c.۳۶۴T>A(p.Tyr۱۲۲Asn) variant. In conclusion, with a threshold of deleterious effects in seven or more in silicopredictive tools, this variant could be accepted as pathogenic. However, for its final classification, it isnecessary to consider the other criteria provided by American College of Medical Genetics and Genomics(ACMG-AMP) guidelines.PhD- SNPg PANTHER PSEP SNPs & GO FATHMM-XF I-Mutant Disease PolyPhen-۲ PROVEAN Mutation Taster CADD SIFT # of tools with pathogenic predictionPathogenic Probably damaging Disease Pathogenic Disease Probably damagingDeleterious Disease causing ۲۵ Damaging ۱۰:۱۰

کلیدواژه ها:

Cystic fibrosis (CF) ، CFTR gene ، In silico analysis