Three affected subjects of family 4 inherited the pathogenic missense variant of CACNA1C in a homozygous manner and represented non-syndromic ID.14 This is in contrast with previous studies that reported heterozygous de novo mutations in this gene can give rise to Timothy syndrome (Table S1.3).20,21 The only frameshift mutation in our cases belonged to family 5 in which a 130 bp deletion was found in another voltage-gated calcium channel named CACNA1G. Here, CACNA1C is linked to Timothy syndrome.