TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14873	44842;44843;44844	chr2:178624663;178624662;178624661	chr2:179489390;179489389;179489388
N2AB	13232	39919;39920;39921	chr2:178624663;178624662;178624661	chr2:179489390;179489389;179489388
N2A	12305	37138;37139;37140	chr2:178624663;178624662;178624661	chr2:179489390;179489389;179489388
N2B	5808	17647;17648;17649	chr2:178624663;178624662;178624661	chr2:179489390;179489389;179489388
Novex-1	5933	18022;18023;18024	chr2:178624663;178624662;178624661	chr2:179489390;179489389;179489388
Novex-2	6000	18223;18224;18225	chr2:178624663;178624662;178624661	chr2:179489390;179489389;179489388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-100
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5445
• 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
E/A	None	None	0.919	D	0.591	0.496	None	gnomAD-4.0.0	1.59391E-06	None	None	None	None	N	None	5.67537E-05	0	None	0	0	None	0	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
E/A	0.2654	likely_benign	0.2666	benign	-0.765	Destabilizing	0.919	D	0.591	neutral	D	0.599327764	None	None	N
E/C	0.9343	likely_pathogenic	0.9392	pathogenic	-0.478	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/D	0.5907	likely_pathogenic	0.5708	pathogenic	-1.082	Destabilizing	0.958	D	0.515	neutral	D	0.549173317	None	None	N
E/F	0.903	likely_pathogenic	0.9055	pathogenic	-0.133	Destabilizing	0.995	D	0.698	prob.neutral	None	None	None	None	N
E/G	0.4553	ambiguous	0.4323	ambiguous	-1.131	Destabilizing	0.988	D	0.667	neutral	D	0.70097365	None	None	N
E/H	0.7953	likely_pathogenic	0.7981	pathogenic	-0.321	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
E/I	0.5716	likely_pathogenic	0.5601	ambiguous	0.233	Stabilizing	0.991	D	0.703	prob.neutral	None	None	None	None	N
E/K	0.4975	ambiguous	0.4919	ambiguous	-0.593	Destabilizing	0.958	D	0.554	neutral	D	0.5417718	None	None	N
E/L	0.689	likely_pathogenic	0.6839	pathogenic	0.233	Stabilizing	0.982	D	0.674	neutral	None	None	None	None	N
E/M	0.6857	likely_pathogenic	0.6819	pathogenic	0.56	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
E/N	0.6959	likely_pathogenic	0.6609	pathogenic	-1.108	Destabilizing	0.991	D	0.656	neutral	None	None	None	None	N
E/P	0.9801	likely_pathogenic	0.975	pathogenic	-0.078	Destabilizing	0.995	D	0.743	deleterious	None	None	None	None	N
E/Q	0.2359	likely_benign	0.2375	benign	-0.964	Destabilizing	0.994	D	0.644	neutral	D	0.546945021	None	None	N
E/R	0.6233	likely_pathogenic	0.6476	pathogenic	-0.25	Destabilizing	0.991	D	0.67	neutral	None	None	None	None	N
E/S	0.3698	ambiguous	0.3579	ambiguous	-1.391	Destabilizing	0.938	D	0.548	neutral	None	None	None	None	N
E/T	0.3127	likely_benign	0.3131	benign	-1.09	Destabilizing	0.086	N	0.387	neutral	None	None	None	None	N
E/V	0.3441	ambiguous	0.3352	benign	-0.078	Destabilizing	0.976	D	0.665	neutral	D	0.577728785	None	None	N
E/W	0.976	likely_pathogenic	0.9797	pathogenic	0.121	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/Y	0.8913	likely_pathogenic	0.8948	pathogenic	0.117	Stabilizing	0.998	D	0.707	prob.neutral	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.