TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33697	101314;101315;101316	chr2:178535526;178535525;178535524	chr2:179400253;179400252;179400251
N2AB	32056	96391;96392;96393	chr2:178535526;178535525;178535524	chr2:179400253;179400252;179400251
N2A	31129	93610;93611;93612	chr2:178535526;178535525;178535524	chr2:179400253;179400252;179400251
N2B	24632	74119;74120;74121	chr2:178535526;178535525;178535524	chr2:179400253;179400252;179400251
Novex-1	24757	74494;74495;74496	chr2:178535526;178535525;178535524	chr2:179400253;179400252;179400251
Novex-2	24824	74695;74696;74697	chr2:178535526;178535525;178535524	chr2:179400253;179400252;179400251
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: Fn3-132
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.7263
• 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/T	rs1691033741	None	0.78	N	0.585	0.179	0.280181792013	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	0.2776	likely_benign	0.3452	ambiguous	-0.032	Destabilizing	0.174	N	0.335	neutral	None	None	None	None	N
K/C	0.6094	likely_pathogenic	0.6895	pathogenic	-0.269	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
K/D	0.6101	likely_pathogenic	0.6777	pathogenic	0.206	Stabilizing	0.991	D	0.647	neutral	None	None	None	None	N
K/E	0.1774	likely_benign	0.2155	benign	0.216	Stabilizing	0.878	D	0.58	neutral	N	0.442791751	None	None	N
K/F	0.6675	likely_pathogenic	0.7349	pathogenic	-0.234	Destabilizing	0.956	D	0.714	prob.delet.	None	None	None	None	N
K/G	0.5374	ambiguous	0.6232	pathogenic	-0.236	Destabilizing	0.94	D	0.622	neutral	None	None	None	None	N
K/H	0.2592	likely_benign	0.3057	benign	-0.522	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
K/I	0.1986	likely_benign	0.2312	benign	0.427	Stabilizing	0.148	N	0.617	neutral	N	0.494471365	None	None	N
K/L	0.2634	likely_benign	0.3375	benign	0.427	Stabilizing	0.001	N	0.44	neutral	None	None	None	None	N
K/M	0.1617	likely_benign	0.1947	benign	0.248	Stabilizing	0.868	D	0.668	neutral	None	None	None	None	N
K/N	0.3724	ambiguous	0.4567	ambiguous	0.197	Stabilizing	0.996	D	0.617	neutral	N	0.514326563	None	None	N
K/P	0.9481	likely_pathogenic	0.9458	pathogenic	0.303	Stabilizing	0.991	D	0.661	neutral	None	None	None	None	N
K/Q	0.1166	likely_benign	0.14	benign	0.014	Stabilizing	0.969	D	0.639	neutral	N	0.460953438	None	None	N
K/R	0.0848	likely_benign	0.0892	benign	-0.036	Destabilizing	0.816	D	0.585	neutral	N	0.41849074	None	None	N
K/S	0.3446	ambiguous	0.4341	ambiguous	-0.343	Destabilizing	0.887	D	0.551	neutral	None	None	None	None	N
K/T	0.1124	likely_benign	0.1373	benign	-0.179	Destabilizing	0.78	D	0.585	neutral	N	0.454256752	None	None	N
K/V	0.1802	likely_benign	0.2274	benign	0.303	Stabilizing	0.008	N	0.413	neutral	None	None	None	None	N
K/W	0.7738	likely_pathogenic	0.8115	pathogenic	-0.219	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
K/Y	0.6212	likely_pathogenic	0.6715	pathogenic	0.14	Stabilizing	0.941	D	0.698	prob.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.