TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21936	66031;66032;66033	chr2:178582997;178582996;178582995	chr2:179447724;179447723;179447722
N2AB	20295	61108;61109;61110	chr2:178582997;178582996;178582995	chr2:179447724;179447723;179447722
N2A	19368	58327;58328;58329	chr2:178582997;178582996;178582995	chr2:179447724;179447723;179447722
N2B	12871	38836;38837;38838	chr2:178582997;178582996;178582995	chr2:179447724;179447723;179447722
Novex-1	12996	39211;39212;39213	chr2:178582997;178582996;178582995	chr2:179447724;179447723;179447722
Novex-2	13063	39412;39413;39414	chr2:178582997;178582996;178582995	chr2:179447724;179447723;179447722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-125
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0697
• 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
I/V	None	None	0.02	N	0.296	0.096	0.298056030225	gnomAD-4.0.0	1.70071E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.05254E-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
I/A	0.9539	likely_pathogenic	0.9492	pathogenic	-2.299	Highly Destabilizing	0.91	D	0.753	deleterious	None	None	None	None	N
I/C	0.9753	likely_pathogenic	0.9735	pathogenic	-2.06	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9997	pathogenic	-1.981	Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
I/E	0.9986	likely_pathogenic	0.9987	pathogenic	-1.827	Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
I/F	0.8081	likely_pathogenic	0.8022	pathogenic	-1.574	Destabilizing	0.991	D	0.723	prob.delet.	N	0.463516474	None	None	N
I/G	0.9966	likely_pathogenic	0.9967	pathogenic	-2.782	Highly Destabilizing	0.993	D	0.866	deleterious	None	None	None	None	N
I/H	0.9989	likely_pathogenic	0.9988	pathogenic	-2.142	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
I/K	0.9972	likely_pathogenic	0.9971	pathogenic	-1.589	Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
I/L	0.2162	likely_benign	0.2189	benign	-0.949	Destabilizing	0.58	D	0.389	neutral	N	0.466750755	None	None	N
I/M	0.3942	ambiguous	0.3941	ambiguous	-1.051	Destabilizing	0.991	D	0.686	prob.neutral	N	0.459757492	None	None	N
I/N	0.9963	likely_pathogenic	0.9961	pathogenic	-1.74	Destabilizing	0.997	D	0.876	deleterious	N	0.483141666	None	None	N
I/P	0.9985	likely_pathogenic	0.9986	pathogenic	-1.375	Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
I/Q	0.9974	likely_pathogenic	0.9974	pathogenic	-1.715	Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
I/R	0.9957	likely_pathogenic	0.9955	pathogenic	-1.26	Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
I/S	0.9938	likely_pathogenic	0.9937	pathogenic	-2.553	Highly Destabilizing	0.991	D	0.838	deleterious	N	0.482888177	None	None	N
I/T	0.9856	likely_pathogenic	0.9847	pathogenic	-2.248	Highly Destabilizing	0.939	D	0.785	deleterious	N	0.482634687	None	None	N
I/V	0.0952	likely_benign	0.0934	benign	-1.375	Destabilizing	0.02	N	0.296	neutral	N	0.448895712	None	None	N
I/W	0.9982	likely_pathogenic	0.9982	pathogenic	-1.768	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
I/Y	0.9908	likely_pathogenic	0.99	pathogenic	-1.497	Destabilizing	0.998	D	0.759	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.