TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31101	93526;93527;93528	chr2:178548325;178548324;178548323	chr2:179413052;179413051;179413050
N2AB	29460	88603;88604;88605	chr2:178548325;178548324;178548323	chr2:179413052;179413051;179413050
N2A	28533	85822;85823;85824	chr2:178548325;178548324;178548323	chr2:179413052;179413051;179413050
N2B	22036	66331;66332;66333	chr2:178548325;178548324;178548323	chr2:179413052;179413051;179413050
Novex-1	22161	66706;66707;66708	chr2:178548325;178548324;178548323	chr2:179413052;179413051;179413050
Novex-2	22228	66907;66908;66909	chr2:178548325;178548324;178548323	chr2:179413052;179413051;179413050
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-114
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3219
• 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
P/T	None	None	0.999	D	0.68	0.38	0.503002171853	gnomAD-4.0.0	2.05257E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79889E-06	0	1.65651E-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
P/A	0.0847	likely_benign	0.0734	benign	-1.601	Destabilizing	0.767	D	0.353	neutral	N	0.471645046	None	None	I
P/C	0.4524	ambiguous	0.4453	ambiguous	-1.065	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
P/D	0.7694	likely_pathogenic	0.7013	pathogenic	-1.63	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/E	0.6457	likely_pathogenic	0.5934	pathogenic	-1.656	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/F	0.5049	ambiguous	0.5017	ambiguous	-1.292	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
P/G	0.3327	likely_benign	0.2966	benign	-1.881	Destabilizing	0.997	D	0.606	neutral	None	None	None	None	I
P/H	0.3679	ambiguous	0.3616	ambiguous	-1.342	Destabilizing	1.0	D	0.787	deleterious	D	0.550382397	None	None	I
P/I	0.4531	ambiguous	0.4158	ambiguous	-0.935	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/K	0.6859	likely_pathogenic	0.6298	pathogenic	-1.33	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
P/L	0.2635	likely_benign	0.2244	benign	-0.935	Destabilizing	0.999	D	0.722	prob.delet.	D	0.525223796	None	None	I
P/M	0.4226	ambiguous	0.4128	ambiguous	-0.717	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
P/N	0.5191	ambiguous	0.4814	ambiguous	-1.099	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/Q	0.3756	ambiguous	0.3627	ambiguous	-1.348	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
P/R	0.507	ambiguous	0.4616	ambiguous	-0.71	Destabilizing	0.999	D	0.768	deleterious	N	0.519907878	None	None	I
P/S	0.1771	likely_benign	0.1532	benign	-1.561	Destabilizing	0.992	D	0.581	neutral	N	0.509107777	None	None	I
P/T	0.1736	likely_benign	0.1594	benign	-1.493	Destabilizing	0.999	D	0.68	prob.neutral	D	0.531517673	None	None	I
P/V	0.3104	likely_benign	0.2862	benign	-1.124	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	I
P/W	0.7504	likely_pathogenic	0.7146	pathogenic	-1.418	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
P/Y	0.5249	ambiguous	0.4986	ambiguous	-1.173	Destabilizing	1.0	D	0.813	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.