TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33599	101020;101021;101022	chr2:178535820;178535819;178535818	chr2:179400547;179400546;179400545
N2AB	31958	96097;96098;96099	chr2:178535820;178535819;178535818	chr2:179400547;179400546;179400545
N2A	31031	93316;93317;93318	chr2:178535820;178535819;178535818	chr2:179400547;179400546;179400545
N2B	24534	73825;73826;73827	chr2:178535820;178535819;178535818	chr2:179400547;179400546;179400545
Novex-1	24659	74200;74201;74202	chr2:178535820;178535819;178535818	chr2:179400547;179400546;179400545
Novex-2	24726	74401;74402;74403	chr2:178535820;178535819;178535818	chr2:179400547;179400546;179400545
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-159
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5835
• 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
L/F	None	None	0.996	N	0.74	0.228	0.332386209738	gnomAD-4.0.0	1.6474E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.96296E-06	0	0
L/I	None	None	0.722	N	0.533	0.17	0.209622950755	gnomAD-4.0.0	1.64738E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.96295E-06	0	0
L/P	rs775361062	-0.116	1.0	N	0.76	0.457	0.721476075706	gnomAD-2.1.1	4.16E-06	None	None	None	None	I	None	6.51E-05	0	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
L/A	0.6714	likely_pathogenic	0.5879	pathogenic	-1.057	Destabilizing	0.992	D	0.681	prob.neutral	None	None	None	None	I
L/C	0.9094	likely_pathogenic	0.8928	pathogenic	-0.87	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
L/D	0.9752	likely_pathogenic	0.9677	pathogenic	-0.322	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
L/E	0.8848	likely_pathogenic	0.843	pathogenic	-0.384	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
L/F	0.4535	ambiguous	0.364	ambiguous	-0.951	Destabilizing	0.996	D	0.74	deleterious	N	0.498327242	None	None	I
L/G	0.9166	likely_pathogenic	0.8883	pathogenic	-1.282	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
L/H	0.8265	likely_pathogenic	0.7935	pathogenic	-0.604	Destabilizing	1.0	D	0.744	deleterious	N	0.461367335	None	None	I
L/I	0.2143	likely_benign	0.1787	benign	-0.56	Destabilizing	0.722	D	0.533	neutral	N	0.495726867	None	None	I
L/K	0.8363	likely_pathogenic	0.8034	pathogenic	-0.597	Destabilizing	0.96	D	0.731	prob.delet.	None	None	None	None	I
L/M	0.1899	likely_benign	0.1674	benign	-0.513	Destabilizing	0.665	D	0.425	neutral	None	None	None	None	I
L/N	0.9129	likely_pathogenic	0.8941	pathogenic	-0.364	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
L/P	0.9	likely_pathogenic	0.8634	pathogenic	-0.692	Destabilizing	1.0	D	0.76	deleterious	N	0.461367335	None	None	I
L/Q	0.6863	likely_pathogenic	0.6267	pathogenic	-0.579	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
L/R	0.7902	likely_pathogenic	0.7515	pathogenic	-0.061	Destabilizing	0.996	D	0.738	prob.delet.	N	0.460606866	None	None	I
L/S	0.8421	likely_pathogenic	0.7838	pathogenic	-0.921	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	I
L/T	0.6439	likely_pathogenic	0.567	pathogenic	-0.864	Destabilizing	0.996	D	0.744	deleterious	None	None	None	None	I
L/V	0.2326	likely_benign	0.1925	benign	-0.692	Destabilizing	0.774	D	0.545	neutral	N	0.442297814	None	None	I
L/W	0.7259	likely_pathogenic	0.6458	pathogenic	-0.947	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
L/Y	0.8403	likely_pathogenic	0.7928	pathogenic	-0.7	Destabilizing	0.987	D	0.757	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.