TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16441	49546;49547;49548	chr2:178614076;178614075;178614074	chr2:179478803;179478802;179478801
N2AB	14800	44623;44624;44625	chr2:178614076;178614075;178614074	chr2:179478803;179478802;179478801
N2A	13873	41842;41843;41844	chr2:178614076;178614075;178614074	chr2:179478803;179478802;179478801
N2B	7376	22351;22352;22353	chr2:178614076;178614075;178614074	chr2:179478803;179478802;179478801
Novex-1	7501	22726;22727;22728	chr2:178614076;178614075;178614074	chr2:179478803;179478802;179478801
Novex-2	7568	22927;22928;22929	chr2:178614076;178614075;178614074	chr2:179478803;179478802;179478801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-6
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.4209
• 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
P/L	rs570251027	None	0.986	N	0.651	0.371	0.570232391912	gnomAD-4.0.0	1.59433E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86241E-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
P/A	0.0707	likely_benign	0.0689	benign	-0.689	Destabilizing	0.908	D	0.542	neutral	N	0.476585042	None	None	N
P/C	0.4216	ambiguous	0.38	ambiguous	-0.699	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/D	0.7092	likely_pathogenic	0.662	pathogenic	-0.3	Destabilizing	0.989	D	0.637	neutral	None	None	None	None	N
P/E	0.4478	ambiguous	0.4163	ambiguous	-0.38	Destabilizing	0.989	D	0.651	prob.neutral	None	None	None	None	N
P/F	0.6479	likely_pathogenic	0.5652	pathogenic	-0.69	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/G	0.3538	ambiguous	0.3209	benign	-0.877	Destabilizing	0.929	D	0.633	neutral	None	None	None	None	N
P/H	0.3143	likely_benign	0.2756	benign	-0.33	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/I	0.3645	ambiguous	0.3112	benign	-0.327	Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
P/K	0.4352	ambiguous	0.3797	ambiguous	-0.584	Destabilizing	0.989	D	0.647	neutral	None	None	None	None	N
P/L	0.2142	likely_benign	0.1778	benign	-0.327	Destabilizing	0.986	D	0.651	prob.neutral	N	0.496015469	None	None	N
P/M	0.4174	ambiguous	0.3603	ambiguous	-0.398	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/N	0.4678	ambiguous	0.409	ambiguous	-0.367	Destabilizing	0.989	D	0.75	deleterious	None	None	None	None	N
P/Q	0.2618	likely_benign	0.229	benign	-0.577	Destabilizing	0.993	D	0.735	deleterious	N	0.468613554	None	None	N
P/R	0.3155	likely_benign	0.2697	benign	-0.059	Destabilizing	0.986	D	0.779	deleterious	N	0.477741333	None	None	N
P/S	0.1372	likely_benign	0.127	benign	-0.798	Destabilizing	0.208	N	0.374	neutral	N	0.461180876	None	None	N
P/T	0.1229	likely_benign	0.1102	benign	-0.77	Destabilizing	0.908	D	0.632	neutral	N	0.47471956	None	None	N
P/V	0.2153	likely_benign	0.1848	benign	-0.411	Destabilizing	0.989	D	0.735	deleterious	None	None	None	None	N
P/W	0.8374	likely_pathogenic	0.787	pathogenic	-0.779	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
P/Y	0.6274	likely_pathogenic	0.5532	ambiguous	-0.485	Destabilizing	1.0	D	0.831	deleterious	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.