TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23574	70945;70946;70947	chr2:178575412;178575411;178575410	chr2:179440139;179440138;179440137
N2AB	21933	66022;66023;66024	chr2:178575412;178575411;178575410	chr2:179440139;179440138;179440137
N2A	21006	63241;63242;63243	chr2:178575412;178575411;178575410	chr2:179440139;179440138;179440137
N2B	14509	43750;43751;43752	chr2:178575412;178575411;178575410	chr2:179440139;179440138;179440137
Novex-1	14634	44125;44126;44127	chr2:178575412;178575411;178575410	chr2:179440139;179440138;179440137
Novex-2	14701	44326;44327;44328	chr2:178575412;178575411;178575410	chr2:179440139;179440138;179440137
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: Fn3-59
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.7125
• 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/R	rs781090352	0.192	0.569	N	0.514	0.173	0.307016933798	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs781090352	0.192	0.569	N	0.514	0.173	0.307016933798	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4394	ambiguous	0.4125	ambiguous	-0.004	Destabilizing	0.904	D	0.585	neutral	None	None	None	None	N
K/C	0.8012	likely_pathogenic	0.7904	pathogenic	-0.252	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
K/D	0.7611	likely_pathogenic	0.7291	pathogenic	0.056	Stabilizing	0.825	D	0.57	neutral	None	None	None	None	N
K/E	0.3086	likely_benign	0.2766	benign	0.074	Stabilizing	0.007	N	0.333	neutral	N	0.472554511	None	None	N
K/F	0.8793	likely_pathogenic	0.8642	pathogenic	-0.129	Destabilizing	0.929	D	0.683	prob.neutral	None	None	None	None	N
K/G	0.6389	likely_pathogenic	0.6139	pathogenic	-0.226	Destabilizing	0.971	D	0.585	neutral	None	None	None	None	N
K/H	0.4337	ambiguous	0.4168	ambiguous	-0.483	Destabilizing	0.991	D	0.57	neutral	None	None	None	None	N
K/I	0.4732	ambiguous	0.426	ambiguous	0.506	Stabilizing	0.269	N	0.684	prob.neutral	N	0.475523068	None	None	N
K/L	0.502	ambiguous	0.4713	ambiguous	0.506	Stabilizing	0.122	N	0.599	neutral	None	None	None	None	N
K/M	0.3507	ambiguous	0.3243	benign	0.244	Stabilizing	0.189	N	0.546	neutral	None	None	None	None	N
K/N	0.5994	likely_pathogenic	0.5448	ambiguous	0.148	Stabilizing	0.962	D	0.519	neutral	N	0.479739803	None	None	N
K/P	0.7132	likely_pathogenic	0.6846	pathogenic	0.365	Stabilizing	0.985	D	0.583	neutral	None	None	None	None	N
K/Q	0.19	likely_benign	0.1821	benign	-0.015	Destabilizing	0.602	D	0.531	neutral	N	0.48710641	None	None	N
K/R	0.0912	likely_benign	0.0906	benign	-0.106	Destabilizing	0.569	D	0.514	neutral	N	0.479232824	None	None	N
K/S	0.5901	likely_pathogenic	0.551	ambiguous	-0.349	Destabilizing	0.904	D	0.537	neutral	None	None	None	None	N
K/T	0.3488	ambiguous	0.3093	benign	-0.177	Destabilizing	0.882	D	0.553	neutral	N	0.501010549	None	None	N
K/V	0.4402	ambiguous	0.4051	ambiguous	0.365	Stabilizing	0.155	N	0.591	neutral	None	None	None	None	N
K/W	0.8547	likely_pathogenic	0.8426	pathogenic	-0.128	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
K/Y	0.7788	likely_pathogenic	0.7514	pathogenic	0.214	Stabilizing	0.905	D	0.673	neutral	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.