TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8156	24691;24692;24693	chr2:178718734;178718733;178718732	chr2:179583461;179583460;179583459
N2AB	7839	23740;23741;23742	chr2:178718734;178718733;178718732	chr2:179583461;179583460;179583459
N2A	6912	20959;20960;20961	chr2:178718734;178718733;178718732	chr2:179583461;179583460;179583459
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-66
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.6309
• Predicted PPI site: I

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
A/P	None	None	1.0	D	0.747	0.563	0.616597772999	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.669	likely_pathogenic	0.6509	pathogenic	-0.803	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
A/D	0.7471	likely_pathogenic	0.6346	pathogenic	-0.509	Destabilizing	1.0	D	0.777	deleterious	N	0.513715447	None	None	I
A/E	0.6531	likely_pathogenic	0.548	ambiguous	-0.66	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
A/F	0.3868	ambiguous	0.3653	ambiguous	-0.918	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
A/G	0.26	likely_benign	0.2577	benign	-0.195	Destabilizing	1.0	D	0.591	neutral	N	0.509547937	None	None	I
A/H	0.7353	likely_pathogenic	0.6744	pathogenic	-0.188	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
A/I	0.3308	likely_benign	0.304	benign	-0.407	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
A/K	0.777	likely_pathogenic	0.6985	pathogenic	-0.472	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
A/L	0.3877	ambiguous	0.3143	benign	-0.407	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
A/M	0.3505	ambiguous	0.3093	benign	-0.535	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
A/N	0.6098	likely_pathogenic	0.5493	ambiguous	-0.169	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/P	0.9367	likely_pathogenic	0.9101	pathogenic	-0.315	Destabilizing	1.0	D	0.747	deleterious	D	0.545809354	None	None	I
A/Q	0.6649	likely_pathogenic	0.5838	pathogenic	-0.437	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/R	0.6559	likely_pathogenic	0.5607	ambiguous	-0.05	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
A/S	0.1451	likely_benign	0.1393	benign	-0.355	Destabilizing	1.0	D	0.632	neutral	N	0.499824247	None	None	I
A/T	0.1683	likely_benign	0.1495	benign	-0.436	Destabilizing	1.0	D	0.706	prob.neutral	N	0.519636795	None	None	I
A/V	0.1383	likely_benign	0.1302	benign	-0.315	Destabilizing	1.0	D	0.67	neutral	N	0.481571931	None	None	I
A/W	0.8887	likely_pathogenic	0.8539	pathogenic	-1.009	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
A/Y	0.6685	likely_pathogenic	0.6316	pathogenic	-0.694	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I

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.