Description
The c.1210-7_1210-6delTT variant in the CFTR gene, also reported as c.1210-12T[5] and commonly referred to as the 5T allele, occurs in the poly T tract in intron 9 (intron 8 using legacy exon numbering). The c.1210-7_1210-6delTT variant acts as a disease susceptibility variant with variable penetrance (CFTR2 Mutation Database; Ong et al., 2017). Specifically, the c.1210-7_1210-6delTT variant has been associated with recessive CFTR-related disorders when seen in trans with another severe pathogenic variant in the CFTR gene. Disease features described include elevated sweat chloride levels, congenital bilateral absence of the vas deferens (CBAVD) in males, and non-classic to classic cystic fibrosis (Chillon et al., 1995; Ong et al., 2017). However, the penetrance of the c.1210-7_1210-6delTT variant is influenced by the presence of other variants (e.g. R117H) and the length of the adjacent TG tract on the same allele (in cis). Longer TG repeat sizes (TG12 and TG13) in cis with c.1210-7_1210-6delTT are associated with a greater susceptibility to disease than c.1210-7_1210-6delTT in cis with a smaller TG repeat size (TG11) (Cuppens et al., 1998; Groman et al., 2004; Ong et al., 2017). RNA studies demonstrate that the c.1210-7_1210-6delTT variant results in abnormal splicing of exon 10 in a significant percentage of transcripts (Chu et al., 1993; Hefferon et al., 2002). The c.1210-7_1210-6delTT variant has been observed in at least 5% of alleles from of individuals of European background (Chillon et al., 1995). Therefore, based on the information available, we interpret c.1210-7_1210-6delTT as a pathogenic susceptibility variant with variable penetrance.
| # | 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 |
