TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26898	80917;80918;80919	chr2:178565440;178565439;178565438	chr2:179430167;179430166;179430165
N2AB	25257	75994;75995;75996	chr2:178565440;178565439;178565438	chr2:179430167;179430166;179430165
N2A	24330	73213;73214;73215	chr2:178565440;178565439;178565438	chr2:179430167;179430166;179430165
N2B	17833	53722;53723;53724	chr2:178565440;178565439;178565438	chr2:179430167;179430166;179430165
Novex-1	17958	54097;54098;54099	chr2:178565440;178565439;178565438	chr2:179430167;179430166;179430165
Novex-2	18025	54298;54299;54300	chr2:178565440;178565439;178565438	chr2:179430167;179430166;179430165
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-139
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.6739
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/N	rs372650410	None	1.0	N	0.735	0.249	0.17948927462	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85951E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.421	ambiguous	0.5057	ambiguous	-0.442	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
K/C	0.5959	likely_pathogenic	0.6844	pathogenic	-0.493	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/D	0.7036	likely_pathogenic	0.7645	pathogenic	-0.222	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/E	0.2571	likely_benign	0.3136	benign	-0.104	Destabilizing	0.999	D	0.604	neutral	N	0.489992974	None	None	N
K/F	0.7686	likely_pathogenic	0.8319	pathogenic	-0.069	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/G	0.6519	likely_pathogenic	0.7155	pathogenic	-0.795	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/H	0.2541	likely_benign	0.2882	benign	-0.981	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/I	0.2979	likely_benign	0.3817	ambiguous	0.467	Stabilizing	1.0	D	0.744	deleterious	N	0.507770658	None	None	N
K/L	0.3422	ambiguous	0.4111	ambiguous	0.467	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/M	0.2107	likely_benign	0.2603	benign	0.09	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.468	ambiguous	0.508	ambiguous	-0.466	Destabilizing	1.0	D	0.735	prob.delet.	N	0.50136476	None	None	N
K/P	0.9084	likely_pathogenic	0.9248	pathogenic	0.193	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/Q	0.1382	likely_benign	0.1564	benign	-0.445	Destabilizing	1.0	D	0.719	prob.delet.	N	0.493283995	None	None	N
K/R	0.088	likely_benign	0.0888	benign	-0.56	Destabilizing	0.999	D	0.546	neutral	N	0.47689039	None	None	N
K/S	0.4574	ambiguous	0.5394	ambiguous	-0.984	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
K/T	0.1505	likely_benign	0.1979	benign	-0.668	Destabilizing	1.0	D	0.729	prob.delet.	N	0.456955048	None	None	N
K/V	0.2794	likely_benign	0.3471	ambiguous	0.193	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/W	0.7302	likely_pathogenic	0.7803	pathogenic	-0.036	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/Y	0.6364	likely_pathogenic	0.707	pathogenic	0.232	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.