TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14751	44476;44477;44478	chr2:178630271;178630270;178630269	chr2:179494998;179494997;179494996
N2AB	13110	39553;39554;39555	chr2:178630271;178630270;178630269	chr2:179494998;179494997;179494996
N2A	12183	36772;36773;36774	chr2:178630271;178630270;178630269	chr2:179494998;179494997;179494996
N2B	5686	17281;17282;17283	chr2:178630271;178630270;178630269	chr2:179494998;179494997;179494996
Novex-1	5811	17656;17657;17658	chr2:178630271;178630270;178630269	chr2:179494998;179494997;179494996
Novex-2	5878	17857;17858;17859	chr2:178630271;178630270;178630269	chr2:179494998;179494997;179494996
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-98
• Domain position: 77
• Structural Position: 162
• Q(SASA): 0.1165
• 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
V/I	rs1293013607	None	0.293	N	0.497	0.147	0.203808441222	gnomAD-4.0.0	6.00162E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	5.25002E-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
V/A	0.1343	likely_benign	0.1638	benign	-1.598	Destabilizing	None	N	0.122	neutral	N	0.339685288	None	None	N
V/C	0.6741	likely_pathogenic	0.7517	pathogenic	-0.998	Destabilizing	0.905	D	0.611	neutral	None	None	None	None	N
V/D	0.7632	likely_pathogenic	0.7999	pathogenic	-1.505	Destabilizing	0.877	D	0.722	deleterious	N	0.43549689	None	None	N
V/E	0.6059	likely_pathogenic	0.6826	pathogenic	-1.412	Destabilizing	0.571	D	0.565	neutral	None	None	None	None	N
V/F	0.3722	ambiguous	0.4677	ambiguous	-1.03	Destabilizing	0.877	D	0.674	prob.neutral	N	0.43782368	None	None	N
V/G	0.3449	ambiguous	0.3999	ambiguous	-2.015	Highly Destabilizing	0.172	N	0.555	neutral	N	0.425785183	None	None	N
V/H	0.8277	likely_pathogenic	0.8844	pathogenic	-1.603	Destabilizing	0.991	D	0.673	prob.neutral	None	None	None	None	N
V/I	0.1087	likely_benign	0.1232	benign	-0.51	Destabilizing	0.293	N	0.497	neutral	N	0.435478575	None	None	N
V/K	0.6695	likely_pathogenic	0.7803	pathogenic	-1.343	Destabilizing	0.571	D	0.567	neutral	None	None	None	None	N
V/L	0.3609	ambiguous	0.4641	ambiguous	-0.51	Destabilizing	0.172	N	0.373	neutral	N	0.423555025	None	None	N
V/M	0.2484	likely_benign	0.3202	benign	-0.389	Destabilizing	0.966	D	0.563	neutral	None	None	None	None	N
V/N	0.5871	likely_pathogenic	0.6634	pathogenic	-1.292	Destabilizing	0.905	D	0.73	deleterious	None	None	None	None	N
V/P	0.9564	likely_pathogenic	0.9735	pathogenic	-0.839	Destabilizing	0.73	D	0.649	prob.neutral	None	None	None	None	N
V/Q	0.5715	likely_pathogenic	0.6777	pathogenic	-1.316	Destabilizing	0.905	D	0.649	prob.neutral	None	None	None	None	N
V/R	0.5725	likely_pathogenic	0.7028	pathogenic	-0.971	Destabilizing	0.905	D	0.739	deleterious	None	None	None	None	N
V/S	0.3013	likely_benign	0.3461	ambiguous	-1.881	Destabilizing	0.216	N	0.481	neutral	None	None	None	None	N
V/T	0.2498	likely_benign	0.2885	benign	-1.66	Destabilizing	0.355	N	0.423	neutral	None	None	None	None	N
V/W	0.9405	likely_pathogenic	0.9617	pathogenic	-1.363	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
V/Y	0.7386	likely_pathogenic	0.8314	pathogenic	-1.01	Destabilizing	0.966	D	0.693	prob.delet.	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.