TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20760	62503;62504;62505	chr2:178589447;178589446;178589445	chr2:179454174;179454173;179454172
N2AB	19119	57580;57581;57582	chr2:178589447;178589446;178589445	chr2:179454174;179454173;179454172
N2A	18192	54799;54800;54801	chr2:178589447;178589446;178589445	chr2:179454174;179454173;179454172
N2B	11695	35308;35309;35310	chr2:178589447;178589446;178589445	chr2:179454174;179454173;179454172
Novex-1	11820	35683;35684;35685	chr2:178589447;178589446;178589445	chr2:179454174;179454173;179454172
Novex-2	11887	35884;35885;35886	chr2:178589447;178589446;178589445	chr2:179454174;179454173;179454172
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-38
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.3594
• 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
V/I	None	None	0.103	N	0.145	0.138	0.323342291347	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.3727	ambiguous	0.3644	ambiguous	-1.511	Destabilizing	0.893	D	0.461	neutral	N	0.475400028	None	None	N
V/C	0.8521	likely_pathogenic	0.8645	pathogenic	-1.029	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/D	0.8818	likely_pathogenic	0.8552	pathogenic	-1.442	Destabilizing	0.998	D	0.867	deleterious	N	0.468646533	None	None	N
V/E	0.7555	likely_pathogenic	0.7274	pathogenic	-1.254	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
V/F	0.4364	ambiguous	0.4434	ambiguous	-0.807	Destabilizing	0.993	D	0.746	deleterious	N	0.489097257	None	None	N
V/G	0.6673	likely_pathogenic	0.6178	pathogenic	-2.001	Highly Destabilizing	0.998	D	0.854	deleterious	N	0.468139554	None	None	N
V/H	0.9124	likely_pathogenic	0.8976	pathogenic	-1.526	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/I	0.0935	likely_benign	0.1001	benign	-0.179	Destabilizing	0.103	N	0.145	neutral	N	0.436169636	None	None	N
V/K	0.8682	likely_pathogenic	0.845	pathogenic	-1.184	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/L	0.4569	ambiguous	0.5009	ambiguous	-0.179	Destabilizing	0.807	D	0.383	neutral	N	0.484211513	None	None	N
V/M	0.2755	likely_benign	0.2975	benign	-0.249	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
V/N	0.7988	likely_pathogenic	0.7493	pathogenic	-1.427	Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
V/P	0.9834	likely_pathogenic	0.9774	pathogenic	-0.592	Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	N
V/Q	0.7953	likely_pathogenic	0.756	pathogenic	-1.28	Destabilizing	0.998	D	0.846	deleterious	None	None	None	None	N
V/R	0.8438	likely_pathogenic	0.8123	pathogenic	-1.054	Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
V/S	0.6607	likely_pathogenic	0.6082	pathogenic	-2.086	Highly Destabilizing	0.998	D	0.693	prob.delet.	None	None	None	None	N
V/T	0.2791	likely_benign	0.2421	benign	-1.742	Destabilizing	0.982	D	0.537	neutral	None	None	None	None	N
V/W	0.9459	likely_pathogenic	0.952	pathogenic	-1.188	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
V/Y	0.8369	likely_pathogenic	0.841	pathogenic	-0.771	Destabilizing	0.998	D	0.728	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.