TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18147	54664;54665;54666	chr2:178604248;178604247;178604246	chr2:179468975;179468974;179468973
N2AB	16506	49741;49742;49743	chr2:178604248;178604247;178604246	chr2:179468975;179468974;179468973
N2A	15579	46960;46961;46962	chr2:178604248;178604247;178604246	chr2:179468975;179468974;179468973
N2B	9082	27469;27470;27471	chr2:178604248;178604247;178604246	chr2:179468975;179468974;179468973
Novex-1	9207	27844;27845;27846	chr2:178604248;178604247;178604246	chr2:179468975;179468974;179468973
Novex-2	9274	28045;28046;28047	chr2:178604248;178604247;178604246	chr2:179468975;179468974;179468973
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: Fn3-19
• Domain position: 83
• Structural Position: 114
• Q(SASA): 0.6323
• 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
Y/N	None	None	1.0	N	0.743	0.441	0.690350978659	gnomAD-4.0.0	6.99584E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.69929E-05

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	0.9077	likely_pathogenic	0.9373	pathogenic	-0.626	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	I
Y/C	0.5484	ambiguous	0.611	pathogenic	0.092	Stabilizing	1.0	D	0.77	deleterious	N	0.50326142	None	None	I
Y/D	0.9021	likely_pathogenic	0.9446	pathogenic	1.035	Stabilizing	1.0	D	0.751	deleterious	N	0.472606098	None	None	I
Y/E	0.9567	likely_pathogenic	0.9746	pathogenic	1.015	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
Y/F	0.1138	likely_benign	0.1123	benign	-0.315	Destabilizing	0.434	N	0.384	neutral	N	0.496084732	None	None	I
Y/G	0.9254	likely_pathogenic	0.9492	pathogenic	-0.81	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
Y/H	0.5928	likely_pathogenic	0.6664	pathogenic	0.24	Stabilizing	1.0	D	0.655	neutral	N	0.51613193	None	None	I
Y/I	0.786	likely_pathogenic	0.806	pathogenic	-0.171	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
Y/K	0.9715	likely_pathogenic	0.9817	pathogenic	0.273	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
Y/L	0.8068	likely_pathogenic	0.849	pathogenic	-0.171	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	I
Y/M	0.8299	likely_pathogenic	0.869	pathogenic	-0.025	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
Y/N	0.6623	likely_pathogenic	0.766	pathogenic	0.108	Stabilizing	1.0	D	0.743	deleterious	N	0.517862726	None	None	I
Y/P	0.9942	likely_pathogenic	0.9948	pathogenic	-0.302	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
Y/Q	0.925	likely_pathogenic	0.953	pathogenic	0.145	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
Y/R	0.9412	likely_pathogenic	0.9574	pathogenic	0.526	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
Y/S	0.8255	likely_pathogenic	0.8889	pathogenic	-0.367	Destabilizing	1.0	D	0.713	prob.delet.	N	0.513803701	None	None	I
Y/T	0.9227	likely_pathogenic	0.9513	pathogenic	-0.293	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
Y/V	0.7265	likely_pathogenic	0.7717	pathogenic	-0.302	Destabilizing	0.997	D	0.663	neutral	None	None	None	None	I
Y/W	0.5575	ambiguous	0.5464	ambiguous	-0.435	Destabilizing	1.0	D	0.651	neutral	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.