TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5524	16795;16796;16797	chr2:178732491;178732490;178732489	chr2:179597218;179597217;179597216
N2AB	5207	15844;15845;15846	chr2:178732491;178732490;178732489	chr2:179597218;179597217;179597216
N2A	4280	13063;13064;13065	chr2:178732491;178732490;178732489	chr2:179597218;179597217;179597216
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-38
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.064
• 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	None	None	0.004	N	0.272	0.134	0.41921206133	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-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	0.4122	ambiguous	0.476	ambiguous	-2.117	Highly Destabilizing	0.581	D	0.603	neutral	N	0.429057237	None	None	N
V/C	0.9637	likely_pathogenic	0.9692	pathogenic	-1.695	Destabilizing	0.993	D	0.866	deleterious	None	None	None	None	N
V/D	0.9917	likely_pathogenic	0.9917	pathogenic	-2.863	Highly Destabilizing	0.908	D	0.884	deleterious	D	0.547422877	None	None	N
V/E	0.9795	likely_pathogenic	0.9796	pathogenic	-2.574	Highly Destabilizing	0.929	D	0.873	deleterious	None	None	None	None	N
V/F	0.7294	likely_pathogenic	0.7502	pathogenic	-1.165	Destabilizing	0.83	D	0.871	deleterious	D	0.535813083	None	None	N
V/G	0.7392	likely_pathogenic	0.7536	pathogenic	-2.724	Highly Destabilizing	0.908	D	0.868	deleterious	N	0.503719176	None	None	N
V/H	0.9955	likely_pathogenic	0.9961	pathogenic	-2.621	Highly Destabilizing	0.993	D	0.882	deleterious	None	None	None	None	N
V/I	0.1051	likely_benign	0.1073	benign	-0.382	Destabilizing	0.004	N	0.272	neutral	N	0.511302979	None	None	N
V/K	0.9915	likely_pathogenic	0.9915	pathogenic	-1.659	Destabilizing	0.929	D	0.873	deleterious	None	None	None	None	N
V/L	0.5059	ambiguous	0.5454	ambiguous	-0.382	Destabilizing	0.09	N	0.601	neutral	N	0.513972618	None	None	N
V/M	0.5655	likely_pathogenic	0.6299	pathogenic	-0.622	Destabilizing	0.866	D	0.831	deleterious	None	None	None	None	N
V/N	0.9746	likely_pathogenic	0.9783	pathogenic	-2.181	Highly Destabilizing	0.976	D	0.908	deleterious	None	None	None	None	N
V/P	0.9915	likely_pathogenic	0.9919	pathogenic	-0.937	Destabilizing	0.976	D	0.881	deleterious	None	None	None	None	N
V/Q	0.9822	likely_pathogenic	0.9832	pathogenic	-1.882	Destabilizing	0.976	D	0.909	deleterious	None	None	None	None	N
V/R	0.9821	likely_pathogenic	0.9803	pathogenic	-1.73	Destabilizing	0.929	D	0.905	deleterious	None	None	None	None	N
V/S	0.8596	likely_pathogenic	0.8894	pathogenic	-2.791	Highly Destabilizing	0.929	D	0.853	deleterious	None	None	None	None	N
V/T	0.782	likely_pathogenic	0.8287	pathogenic	-2.34	Highly Destabilizing	0.648	D	0.696	prob.neutral	None	None	None	None	N
V/W	0.9962	likely_pathogenic	0.9967	pathogenic	-1.749	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9715	likely_pathogenic	0.9729	pathogenic	-1.355	Destabilizing	0.929	D	0.87	deleterious	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.