TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24826	74701;74702;74703	chr2:178571656;178571655;178571654	chr2:179436383;179436382;179436381
N2AB	23185	69778;69779;69780	chr2:178571656;178571655;178571654	chr2:179436383;179436382;179436381
N2A	22258	66997;66998;66999	chr2:178571656;178571655;178571654	chr2:179436383;179436382;179436381
N2B	15761	47506;47507;47508	chr2:178571656;178571655;178571654	chr2:179436383;179436382;179436381
Novex-1	15886	47881;47882;47883	chr2:178571656;178571655;178571654	chr2:179436383;179436382;179436381
Novex-2	15953	48082;48083;48084	chr2:178571656;178571655;178571654	chr2:179436383;179436382;179436381
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: Fn3-68
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.0704
• 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/N	rs764053971	-3.014	0.741	N	0.811	0.44	0.838227082898	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/N	rs764053971	-3.014	0.741	N	0.811	0.44	0.838227082898	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.6868	likely_pathogenic	0.6816	pathogenic	-2.928	Highly Destabilizing	0.035	N	0.621	neutral	None	None	None	None	N
I/C	0.7239	likely_pathogenic	0.7061	pathogenic	-2.788	Highly Destabilizing	0.001	N	0.559	neutral	None	None	None	None	N
I/D	0.9947	likely_pathogenic	0.995	pathogenic	-3.394	Highly Destabilizing	0.555	D	0.811	deleterious	None	None	None	None	N
I/E	0.9847	likely_pathogenic	0.9865	pathogenic	-3.155	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/F	0.4205	ambiguous	0.4134	ambiguous	-1.789	Destabilizing	0.317	N	0.733	prob.delet.	N	0.471221108	None	None	N
I/G	0.9659	likely_pathogenic	0.964	pathogenic	-3.467	Highly Destabilizing	0.555	D	0.778	deleterious	None	None	None	None	N
I/H	0.9755	likely_pathogenic	0.9778	pathogenic	-2.787	Highly Destabilizing	0.935	D	0.777	deleterious	None	None	None	None	N
I/K	0.9656	likely_pathogenic	0.9689	pathogenic	-2.259	Highly Destabilizing	0.555	D	0.798	deleterious	None	None	None	None	N
I/L	0.1417	likely_benign	0.1344	benign	-1.349	Destabilizing	None	N	0.286	neutral	N	0.462028086	None	None	N
I/M	0.1222	likely_benign	0.1202	benign	-1.7	Destabilizing	0.317	N	0.663	neutral	N	0.510152894	None	None	N
I/N	0.9357	likely_pathogenic	0.9397	pathogenic	-2.717	Highly Destabilizing	0.741	D	0.811	deleterious	N	0.506468567	None	None	N
I/P	0.9959	likely_pathogenic	0.995	pathogenic	-1.86	Destabilizing	0.791	D	0.815	deleterious	None	None	None	None	N
I/Q	0.9608	likely_pathogenic	0.9631	pathogenic	-2.573	Highly Destabilizing	0.791	D	0.799	deleterious	None	None	None	None	N
I/R	0.9475	likely_pathogenic	0.9507	pathogenic	-1.97	Destabilizing	0.555	D	0.813	deleterious	None	None	None	None	N
I/S	0.8673	likely_pathogenic	0.8717	pathogenic	-3.427	Highly Destabilizing	0.117	N	0.758	deleterious	N	0.506215077	None	None	N
I/T	0.7901	likely_pathogenic	0.7945	pathogenic	-3.036	Highly Destabilizing	0.062	N	0.733	prob.delet.	N	0.499378222	None	None	N
I/V	0.0603	likely_benign	0.064	benign	-1.86	Destabilizing	None	N	0.199	neutral	N	0.393704151	None	None	N
I/W	0.979	likely_pathogenic	0.9773	pathogenic	-2.067	Highly Destabilizing	0.935	D	0.772	deleterious	None	None	None	None	N
I/Y	0.8986	likely_pathogenic	0.8999	pathogenic	-1.883	Destabilizing	0.555	D	0.813	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.