TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3176	9751;9752;9753	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283
N2AB	3176	9751;9752;9753	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283
N2A	3176	9751;9752;9753	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283
N2B	3130	9613;9614;9615	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283
Novex-1	3130	9613;9614;9615	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283
Novex-2	3130	9613;9614;9615	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283
Novex-3	3176	9751;9752;9753	chr2:178766558;178766557;178766556	chr2:179631285;179631284;179631283

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-22
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.4836
• 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	None	None	0.997	N	0.743	0.642	0.73228921728	gnomAD-4.0.0	1.59065E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88232E-05	0	0	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	0.3716	ambiguous	0.4066	ambiguous	-0.02	Destabilizing	0.939	D	0.601	neutral	N	0.496480625	None	None	N
D/C	0.9319	likely_pathogenic	0.941	pathogenic	-0.068	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
D/E	0.2712	likely_benign	0.2926	benign	-0.064	Destabilizing	0.02	N	0.23	neutral	N	0.408944719	None	None	N
D/F	0.8495	likely_pathogenic	0.8742	pathogenic	-0.141	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
D/G	0.5069	ambiguous	0.5659	pathogenic	-0.145	Destabilizing	0.939	D	0.619	neutral	N	0.511777351	None	None	N
D/H	0.6606	likely_pathogenic	0.6924	pathogenic	0.345	Stabilizing	0.998	D	0.706	prob.neutral	N	0.511265133	None	None	N
D/I	0.6812	likely_pathogenic	0.7205	pathogenic	0.244	Stabilizing	0.993	D	0.754	deleterious	None	None	None	None	N
D/K	0.7495	likely_pathogenic	0.7859	pathogenic	0.296	Stabilizing	0.91	D	0.58	neutral	None	None	None	None	N
D/L	0.6593	likely_pathogenic	0.6931	pathogenic	0.244	Stabilizing	0.986	D	0.747	deleterious	None	None	None	None	N
D/M	0.865	likely_pathogenic	0.8819	pathogenic	0.082	Stabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
D/N	0.239	likely_benign	0.2707	benign	0.294	Stabilizing	0.939	D	0.528	neutral	N	0.510546257	None	None	N
D/P	0.8212	likely_pathogenic	0.8393	pathogenic	0.176	Stabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
D/Q	0.6823	likely_pathogenic	0.715	pathogenic	0.284	Stabilizing	0.973	D	0.571	neutral	None	None	None	None	N
D/R	0.7701	likely_pathogenic	0.7967	pathogenic	0.526	Stabilizing	0.986	D	0.753	deleterious	None	None	None	None	N
D/S	0.3006	likely_benign	0.3346	benign	0.108	Stabilizing	0.953	D	0.471	neutral	None	None	None	None	N
D/T	0.5157	ambiguous	0.5474	ambiguous	0.199	Stabilizing	0.986	D	0.653	neutral	None	None	None	None	N
D/V	0.4584	ambiguous	0.4937	ambiguous	0.176	Stabilizing	0.991	D	0.735	prob.delet.	N	0.510546257	None	None	N
D/W	0.976	likely_pathogenic	0.9771	pathogenic	-0.111	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
D/Y	0.5556	ambiguous	0.5925	pathogenic	0.076	Stabilizing	0.997	D	0.743	deleterious	N	0.512309973	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.