TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20012	60259;60260;60261	chr2:178591785;178591784;178591783	chr2:179456512;179456511;179456510
N2AB	18371	55336;55337;55338	chr2:178591785;178591784;178591783	chr2:179456512;179456511;179456510
N2A	17444	52555;52556;52557	chr2:178591785;178591784;178591783	chr2:179456512;179456511;179456510
N2B	10947	33064;33065;33066	chr2:178591785;178591784;178591783	chr2:179456512;179456511;179456510
Novex-1	11072	33439;33440;33441	chr2:178591785;178591784;178591783	chr2:179456512;179456511;179456510
Novex-2	11139	33640;33641;33642	chr2:178591785;178591784;178591783	chr2:179456512;179456511;179456510
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-33
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1087
• 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
Y/H	None	None	0.995	D	0.713	0.782	0.792734160242	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	5.65995E-05	0	None	0	0	None	0	0	0	0	0
Y/N	None	None	0.995	D	0.863	0.765	0.932797117025	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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
Y/A	0.9973	likely_pathogenic	0.9981	pathogenic	-3.364	Highly Destabilizing	0.959	D	0.789	deleterious	None	None	None	None	N
Y/C	0.916	likely_pathogenic	0.9493	pathogenic	-1.932	Destabilizing	0.999	D	0.861	deleterious	D	0.645386919	None	None	N
Y/D	0.9957	likely_pathogenic	0.9966	pathogenic	-3.833	Highly Destabilizing	0.995	D	0.883	deleterious	D	0.645588724	None	None	N
Y/E	0.9989	likely_pathogenic	0.9992	pathogenic	-3.609	Highly Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
Y/F	0.1973	likely_benign	0.2381	benign	-1.246	Destabilizing	0.011	N	0.327	neutral	D	0.547564474	None	None	N
Y/G	0.9924	likely_pathogenic	0.994	pathogenic	-3.787	Highly Destabilizing	0.988	D	0.836	deleterious	None	None	None	None	N
Y/H	0.9718	likely_pathogenic	0.9826	pathogenic	-2.498	Highly Destabilizing	0.995	D	0.713	prob.delet.	D	0.62896395	None	None	N
Y/I	0.9631	likely_pathogenic	0.973	pathogenic	-1.935	Destabilizing	0.851	D	0.784	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9989	pathogenic	-2.405	Highly Destabilizing	0.996	D	0.842	deleterious	None	None	None	None	N
Y/L	0.9348	likely_pathogenic	0.9532	pathogenic	-1.935	Destabilizing	0.702	D	0.756	deleterious	None	None	None	None	N
Y/M	0.9791	likely_pathogenic	0.9861	pathogenic	-1.717	Destabilizing	0.988	D	0.815	deleterious	None	None	None	None	N
Y/N	0.9743	likely_pathogenic	0.9799	pathogenic	-3.247	Highly Destabilizing	0.995	D	0.863	deleterious	D	0.645386919	None	None	N
Y/P	0.9994	likely_pathogenic	0.9995	pathogenic	-2.431	Highly Destabilizing	0.996	D	0.882	deleterious	None	None	None	None	N
Y/Q	0.9981	likely_pathogenic	0.9986	pathogenic	-2.962	Highly Destabilizing	0.996	D	0.797	deleterious	None	None	None	None	N
Y/R	0.9947	likely_pathogenic	0.996	pathogenic	-2.228	Highly Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
Y/S	0.9875	likely_pathogenic	0.9911	pathogenic	-3.551	Highly Destabilizing	0.984	D	0.806	deleterious	D	0.645386919	None	None	N
Y/T	0.9957	likely_pathogenic	0.997	pathogenic	-3.201	Highly Destabilizing	0.988	D	0.804	deleterious	None	None	None	None	N
Y/V	0.9559	likely_pathogenic	0.9665	pathogenic	-2.431	Highly Destabilizing	0.919	D	0.758	deleterious	None	None	None	None	N
Y/W	0.8268	likely_pathogenic	0.8634	pathogenic	-0.474	Destabilizing	0.996	D	0.727	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.