TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23759	71500;71501;71502	chr2:178574857;178574856;178574855	chr2:179439584;179439583;179439582
N2AB	22118	66577;66578;66579	chr2:178574857;178574856;178574855	chr2:179439584;179439583;179439582
N2A	21191	63796;63797;63798	chr2:178574857;178574856;178574855	chr2:179439584;179439583;179439582
N2B	14694	44305;44306;44307	chr2:178574857;178574856;178574855	chr2:179439584;179439583;179439582
Novex-1	14819	44680;44681;44682	chr2:178574857;178574856;178574855	chr2:179439584;179439583;179439582
Novex-2	14886	44881;44882;44883	chr2:178574857;178574856;178574855	chr2:179439584;179439583;179439582
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-60
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2465
• 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
I/L	None	None	0.426	N	0.406	0.212	0.477065420593	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	rs751178599	-1.447	0.011	N	0.223	0.118	0.415947407303	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	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	0.9638	likely_pathogenic	0.9686	pathogenic	-2.265	Highly Destabilizing	0.845	D	0.615	neutral	None	None	None	None	I
I/C	0.9768	likely_pathogenic	0.9795	pathogenic	-1.365	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
I/D	0.9991	likely_pathogenic	0.9994	pathogenic	-2.236	Highly Destabilizing	0.996	D	0.788	deleterious	None	None	None	None	I
I/E	0.9965	likely_pathogenic	0.9975	pathogenic	-2.178	Highly Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	I
I/F	0.9321	likely_pathogenic	0.94	pathogenic	-1.636	Destabilizing	0.975	D	0.739	prob.delet.	None	None	None	None	I
I/G	0.9967	likely_pathogenic	0.9974	pathogenic	-2.662	Highly Destabilizing	0.987	D	0.778	deleterious	None	None	None	None	I
I/H	0.997	likely_pathogenic	0.9976	pathogenic	-1.989	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
I/K	0.9918	likely_pathogenic	0.993	pathogenic	-1.695	Destabilizing	0.983	D	0.78	deleterious	D	0.526439835	None	None	I
I/L	0.3325	likely_benign	0.3517	ambiguous	-1.192	Destabilizing	0.426	N	0.406	neutral	N	0.506421942	None	None	I
I/M	0.6043	likely_pathogenic	0.6205	pathogenic	-0.813	Destabilizing	0.983	D	0.718	prob.delet.	N	0.504688275	None	None	I
I/N	0.9845	likely_pathogenic	0.9869	pathogenic	-1.61	Destabilizing	0.996	D	0.797	deleterious	None	None	None	None	I
I/P	0.9732	likely_pathogenic	0.9752	pathogenic	-1.523	Destabilizing	0.996	D	0.795	deleterious	None	None	None	None	I
I/Q	0.9942	likely_pathogenic	0.9953	pathogenic	-1.746	Destabilizing	0.996	D	0.79	deleterious	None	None	None	None	I
I/R	0.9887	likely_pathogenic	0.9906	pathogenic	-1.08	Destabilizing	0.983	D	0.799	deleterious	D	0.53779614	None	None	I
I/S	0.9819	likely_pathogenic	0.9853	pathogenic	-2.218	Highly Destabilizing	0.987	D	0.747	deleterious	None	None	None	None	I
I/T	0.9406	likely_pathogenic	0.9495	pathogenic	-2.042	Highly Destabilizing	0.892	D	0.718	prob.delet.	N	0.507575111	None	None	I
I/V	0.0899	likely_benign	0.0938	benign	-1.523	Destabilizing	0.011	N	0.223	neutral	N	0.459494787	None	None	I
I/W	0.9991	likely_pathogenic	0.9991	pathogenic	-1.85	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
I/Y	0.9936	likely_pathogenic	0.9949	pathogenic	-1.627	Destabilizing	0.987	D	0.749	deleterious	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.