TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1780	5563;5564;5565	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251
N2AB	1780	5563;5564;5565	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251
N2A	1780	5563;5564;5565	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251
N2B	1734	5425;5426;5427	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251
Novex-1	1734	5425;5426;5427	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251
Novex-2	1734	5425;5426;5427	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251
Novex-3	1780	5563;5564;5565	chr2:178776526;178776525;178776524	chr2:179641253;179641252;179641251

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-8
• Domain position: 78
• Structural Position: 159
• Q(SASA): 0.2419
• 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
T/I	None	None	0.864	N	0.767	0.344	0.595273823551	gnomAD-4.0.0	1.60137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.1421	likely_benign	0.1431	benign	-0.721	Destabilizing	0.273	N	0.572	neutral	D	0.568309209	None	None	I
T/C	0.7445	likely_pathogenic	0.702	pathogenic	-0.678	Destabilizing	0.985	D	0.755	deleterious	None	None	None	None	I
T/D	0.7905	likely_pathogenic	0.8274	pathogenic	-1.438	Destabilizing	0.894	D	0.675	prob.neutral	None	None	None	None	I
T/E	0.6604	likely_pathogenic	0.6936	pathogenic	-1.398	Destabilizing	0.809	D	0.688	prob.neutral	None	None	None	None	I
T/F	0.5868	likely_pathogenic	0.6519	pathogenic	-0.79	Destabilizing	0.945	D	0.823	deleterious	None	None	None	None	I
T/G	0.3876	ambiguous	0.39	ambiguous	-1.004	Destabilizing	0.547	D	0.688	prob.neutral	None	None	None	None	I
T/H	0.5229	ambiguous	0.5352	ambiguous	-1.352	Destabilizing	0.985	D	0.798	deleterious	None	None	None	None	I
T/I	0.4848	ambiguous	0.5017	ambiguous	-0.044	Destabilizing	0.864	D	0.767	deleterious	N	0.518465198	None	None	I
T/K	0.5502	ambiguous	0.5228	ambiguous	-0.835	Destabilizing	0.809	D	0.684	prob.neutral	None	None	None	None	I
T/L	0.3697	ambiguous	0.384	ambiguous	-0.044	Destabilizing	0.707	D	0.642	neutral	None	None	None	None	I
T/M	0.2416	likely_benign	0.2491	benign	0.297	Stabilizing	0.995	D	0.757	deleterious	None	None	None	None	I
T/N	0.2844	likely_benign	0.3133	benign	-1.096	Destabilizing	0.761	D	0.714	prob.delet.	D	0.645829656	None	None	I
T/P	0.8941	likely_pathogenic	0.9076	pathogenic	-0.237	Destabilizing	0.928	D	0.77	deleterious	D	0.697827515	None	None	I
T/Q	0.4371	ambiguous	0.4349	ambiguous	-1.284	Destabilizing	0.894	D	0.777	deleterious	None	None	None	None	I
T/R	0.4735	ambiguous	0.4411	ambiguous	-0.588	Destabilizing	0.894	D	0.777	deleterious	None	None	None	None	I
T/S	0.1274	likely_benign	0.1249	benign	-1.191	Destabilizing	0.006	N	0.259	neutral	N	0.505656212	None	None	I
T/V	0.3024	likely_benign	0.3059	benign	-0.237	Destabilizing	0.707	D	0.652	neutral	None	None	None	None	I
T/W	0.8775	likely_pathogenic	0.8901	pathogenic	-0.837	Destabilizing	0.995	D	0.797	deleterious	None	None	None	None	I
T/Y	0.6287	likely_pathogenic	0.6808	pathogenic	-0.52	Destabilizing	0.945	D	0.819	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.