TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24082	72469;72470;72471	chr2:178573888;178573887;178573886	chr2:179438615;179438614;179438613
N2AB	22441	67546;67547;67548	chr2:178573888;178573887;178573886	chr2:179438615;179438614;179438613
N2A	21514	64765;64766;64767	chr2:178573888;178573887;178573886	chr2:179438615;179438614;179438613
N2B	15017	45274;45275;45276	chr2:178573888;178573887;178573886	chr2:179438615;179438614;179438613
Novex-1	15142	45649;45650;45651	chr2:178573888;178573887;178573886	chr2:179438615;179438614;179438613
Novex-2	15209	45850;45851;45852	chr2:178573888;178573887;178573886	chr2:179438615;179438614;179438613
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-131
• Domain position: 54
• Structural Position: 131
• Q(SASA): 1.0282
• 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/E	None	None	1.0	N	0.419	0.261	0.203808441222	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
D/A	0.22	likely_benign	0.1792	benign	-0.185	Destabilizing	1.0	D	0.619	neutral	N	0.45703524	None	None	N
D/C	0.7797	likely_pathogenic	0.7061	pathogenic	-0.17	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/E	0.2469	likely_benign	0.1922	benign	-0.317	Destabilizing	1.0	D	0.419	neutral	N	0.488800895	None	None	N
D/F	0.7545	likely_pathogenic	0.7046	pathogenic	0.04	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
D/G	0.2269	likely_benign	0.1789	benign	-0.394	Destabilizing	1.0	D	0.617	neutral	N	0.467556044	None	None	N
D/H	0.4627	ambiguous	0.3632	ambiguous	0.399	Stabilizing	1.0	D	0.618	neutral	N	0.466024916	None	None	N
D/I	0.5129	ambiguous	0.431	ambiguous	0.322	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
D/K	0.5793	likely_pathogenic	0.4546	ambiguous	0.306	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
D/L	0.5247	ambiguous	0.4578	ambiguous	0.322	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/M	0.7584	likely_pathogenic	0.6985	pathogenic	0.234	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
D/N	0.145	likely_benign	0.1221	benign	-0.148	Destabilizing	1.0	D	0.585	neutral	N	0.488608894	None	None	N
D/P	0.5518	ambiguous	0.444	ambiguous	0.175	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
D/Q	0.534	ambiguous	0.4232	ambiguous	-0.077	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
D/R	0.5861	likely_pathogenic	0.4706	ambiguous	0.599	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
D/S	0.1794	likely_benign	0.1485	benign	-0.231	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
D/T	0.3721	ambiguous	0.3094	benign	-0.055	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
D/V	0.3258	likely_benign	0.2755	benign	0.175	Stabilizing	1.0	D	0.684	prob.neutral	N	0.487104912	None	None	N
D/W	0.9387	likely_pathogenic	0.9147	pathogenic	0.197	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
D/Y	0.3352	likely_benign	0.2704	benign	0.291	Stabilizing	1.0	D	0.658	neutral	N	0.483484061	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.