TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2727	8404;8405;8406	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338
N2AB	2727	8404;8405;8406	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338
N2A	2727	8404;8405;8406	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338
N2B	2681	8266;8267;8268	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338
Novex-1	2681	8266;8267;8268	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338
Novex-2	2681	8266;8267;8268	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338
Novex-3	2727	8404;8405;8406	chr2:178770613;178770612;178770611	chr2:179635340;179635339;179635338

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-17
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3024
• 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
T/A	None	None	None	D	0.197	0.088	0.220303561663	gnomAD-4.0.0	1.36817E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79859E-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
T/A	0.0854	likely_benign	0.0805	benign	-0.957	Destabilizing	None	N	0.197	neutral	D	0.56079042	None	None	N
T/C	0.3823	ambiguous	0.379	ambiguous	-0.487	Destabilizing	0.824	D	0.545	neutral	None	None	None	None	N
T/D	0.2985	likely_benign	0.2909	benign	-0.067	Destabilizing	0.081	N	0.49	neutral	None	None	None	None	N
T/E	0.2307	likely_benign	0.2392	benign	0.063	Stabilizing	0.081	N	0.461	neutral	None	None	None	None	N
T/F	0.2351	likely_benign	0.2352	benign	-0.797	Destabilizing	0.555	D	0.597	neutral	None	None	None	None	N
T/G	0.2598	likely_benign	0.2328	benign	-1.323	Destabilizing	0.035	N	0.526	neutral	None	None	None	None	N
T/H	0.2398	likely_benign	0.2353	benign	-1.359	Destabilizing	0.824	D	0.582	neutral	None	None	None	None	N
T/I	0.1618	likely_benign	0.165	benign	-0.029	Destabilizing	0.317	N	0.537	neutral	N	0.510104585	None	None	N
T/K	0.2502	likely_benign	0.2546	benign	-0.194	Destabilizing	0.081	N	0.461	neutral	None	None	None	None	N
T/L	0.1069	likely_benign	0.1093	benign	-0.029	Destabilizing	0.081	N	0.492	neutral	None	None	None	None	N
T/M	0.0971	likely_benign	0.0925	benign	-0.031	Destabilizing	0.791	D	0.549	neutral	None	None	None	None	N
T/N	0.1129	likely_benign	0.1096	benign	-0.557	Destabilizing	0.062	N	0.474	neutral	N	0.503744805	None	None	N
T/P	0.3489	ambiguous	0.3635	ambiguous	-0.305	Destabilizing	0.317	N	0.542	neutral	D	0.564047755	None	None	N
T/Q	0.2227	likely_benign	0.2095	benign	-0.45	Destabilizing	0.38	N	0.555	neutral	None	None	None	None	N
T/R	0.2001	likely_benign	0.1993	benign	-0.283	Destabilizing	0.38	N	0.543	neutral	None	None	None	None	N
T/S	0.0892	likely_benign	0.084	benign	-0.96	Destabilizing	None	N	0.222	neutral	N	0.439804904	None	None	N
T/V	0.1347	likely_benign	0.1377	benign	-0.305	Destabilizing	0.081	N	0.487	neutral	None	None	None	None	N
T/W	0.5956	likely_pathogenic	0.5608	ambiguous	-0.78	Destabilizing	0.935	D	0.618	neutral	None	None	None	None	N
T/Y	0.2859	likely_benign	0.2734	benign	-0.452	Destabilizing	0.555	D	0.593	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.