The sequence variant c.1026+2A>G is located in the donor splice site of intron 7 and interferes with the splicing process. In fibroblasts, the variant causes alternative splicing where either the last 12 nucleotides of exon 7 are deleted from the transcript (r.1015–1026del12), or where the last 12 nts of exon 7 are deleted AND the first 3 nucleotides of intron 7 are included (r.1015_1023del9). Both events result in truncated proteins where 3 and 4 aminoacids are missing, respectively (p.Val339–Ala341del3; p.Val339_Gln342del4). Studies in transfected cells show that p.Val339_Gln342del4 is inactive, not processed and retained in the ER.

NOTE: All patients carrying this variant also carries the benign missense mutation p.Glu402Lys.