TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8225	24898;24899;24900	chr2:178718433;178718432;178718431	chr2:179583160;179583159;179583158
N2AB	7908	23947;23948;23949	chr2:178718433;178718432;178718431	chr2:179583160;179583159;179583158
N2A	6981	21166;21167;21168	chr2:178718433;178718432;178718431	chr2:179583160;179583159;179583158
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-67
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2174
• 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
S/F	None	None	0.988	N	0.597	0.394	0.745417300091	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
S/A	0.1553	likely_benign	0.1542	benign	-0.702	Destabilizing	0.906	D	0.441	neutral	N	0.503570002	None	None	N
S/C	0.3074	likely_benign	0.3088	benign	-0.555	Destabilizing	0.999	D	0.541	neutral	N	0.517118808	None	None	N
S/D	0.7905	likely_pathogenic	0.8091	pathogenic	-0.667	Destabilizing	0.984	D	0.516	neutral	None	None	None	None	N
S/E	0.8197	likely_pathogenic	0.8303	pathogenic	-0.63	Destabilizing	0.984	D	0.492	neutral	None	None	None	None	N
S/F	0.515	ambiguous	0.5582	ambiguous	-0.772	Destabilizing	0.988	D	0.597	neutral	N	0.48897492	None	None	N
S/G	0.2419	likely_benign	0.2379	benign	-0.986	Destabilizing	0.984	D	0.463	neutral	None	None	None	None	N
S/H	0.6493	likely_pathogenic	0.672	pathogenic	-1.5	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
S/I	0.448	ambiguous	0.5292	ambiguous	-0.042	Destabilizing	0.939	D	0.581	neutral	None	None	None	None	N
S/K	0.9102	likely_pathogenic	0.9265	pathogenic	-0.711	Destabilizing	0.984	D	0.488	neutral	None	None	None	None	N
S/L	0.262	likely_benign	0.3073	benign	-0.042	Destabilizing	0.088	N	0.356	neutral	None	None	None	None	N
S/M	0.3568	ambiguous	0.3987	ambiguous	0.157	Stabilizing	0.991	D	0.576	neutral	None	None	None	None	N
S/N	0.3266	likely_benign	0.3601	ambiguous	-0.823	Destabilizing	0.995	D	0.532	neutral	None	None	None	None	N
S/P	0.9712	likely_pathogenic	0.9744	pathogenic	-0.227	Destabilizing	0.068	N	0.299	neutral	N	0.510117368	None	None	N
S/Q	0.7569	likely_pathogenic	0.771	pathogenic	-0.918	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
S/R	0.8846	likely_pathogenic	0.8965	pathogenic	-0.697	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
S/T	0.1096	likely_benign	0.1376	benign	-0.741	Destabilizing	0.979	D	0.481	neutral	N	0.481494573	None	None	N
S/V	0.3985	ambiguous	0.4454	ambiguous	-0.227	Destabilizing	0.939	D	0.559	neutral	None	None	None	None	N
S/W	0.7013	likely_pathogenic	0.731	pathogenic	-0.818	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
S/Y	0.3995	ambiguous	0.4308	ambiguous	-0.513	Destabilizing	0.998	D	0.609	neutral	D	0.534406338	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.