TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15451	46576;46577;46578	chr2:178620066;178620065;178620064	chr2:179484793;179484792;179484791
N2AB	13810	41653;41654;41655	chr2:178620066;178620065;178620064	chr2:179484793;179484792;179484791
N2A	12883	38872;38873;38874	chr2:178620066;178620065;178620064	chr2:179484793;179484792;179484791
N2B	6386	19381;19382;19383	chr2:178620066;178620065;178620064	chr2:179484793;179484792;179484791
Novex-1	6511	19756;19757;19758	chr2:178620066;178620065;178620064	chr2:179484793;179484792;179484791
Novex-2	6578	19957;19958;19959	chr2:178620066;178620065;178620064	chr2:179484793;179484792;179484791
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-106
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.4491
• 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
D/Y	rs1576541228	None	0.999	D	0.675	0.665	0.891608219599	gnomAD-4.0.0	4.10974E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.40103E-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
D/A	0.4453	ambiguous	0.5316	ambiguous	-0.825	Destabilizing	0.978	D	0.491	neutral	D	0.538815869	None	None	N
D/C	0.9121	likely_pathogenic	0.9396	pathogenic	-0.377	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
D/E	0.2561	likely_benign	0.2938	benign	-0.813	Destabilizing	0.198	N	0.249	neutral	N	0.488750718	None	None	N
D/F	0.84	likely_pathogenic	0.8814	pathogenic	-0.641	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
D/G	0.3684	ambiguous	0.4201	ambiguous	-1.135	Destabilizing	0.989	D	0.442	neutral	D	0.53513187	None	None	N
D/H	0.665	likely_pathogenic	0.7416	pathogenic	-0.925	Destabilizing	1.0	D	0.489	neutral	D	0.547341546	None	None	N
D/I	0.8228	likely_pathogenic	0.8772	pathogenic	-0.013	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
D/K	0.7623	likely_pathogenic	0.8114	pathogenic	-0.64	Destabilizing	0.983	D	0.421	neutral	None	None	None	None	N
D/L	0.783	likely_pathogenic	0.8343	pathogenic	-0.013	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
D/M	0.8882	likely_pathogenic	0.9247	pathogenic	0.53	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
D/N	0.1968	likely_benign	0.224	benign	-0.996	Destabilizing	0.989	D	0.423	neutral	N	0.50816475	None	None	N
D/P	0.9747	likely_pathogenic	0.9856	pathogenic	-0.26	Destabilizing	0.999	D	0.483	neutral	None	None	None	None	N
D/Q	0.6328	likely_pathogenic	0.7013	pathogenic	-0.893	Destabilizing	0.995	D	0.406	neutral	None	None	None	None	N
D/R	0.7608	likely_pathogenic	0.8207	pathogenic	-0.47	Destabilizing	0.995	D	0.6	neutral	None	None	None	None	N
D/S	0.3413	ambiguous	0.4192	ambiguous	-1.226	Destabilizing	0.983	D	0.395	neutral	None	None	None	None	N
D/T	0.6297	likely_pathogenic	0.7146	pathogenic	-0.978	Destabilizing	0.998	D	0.436	neutral	None	None	None	None	N
D/V	0.6251	likely_pathogenic	0.716	pathogenic	-0.26	Destabilizing	0.997	D	0.67	neutral	D	0.544169316	None	None	N
D/W	0.9598	likely_pathogenic	0.9728	pathogenic	-0.484	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/Y	0.4266	ambiguous	0.4348	ambiguous	-0.435	Destabilizing	0.999	D	0.675	prob.neutral	D	0.662016656	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.