TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20403	61432;61433;61434	chr2:178590518;178590517;178590516	chr2:179455245;179455244;179455243
N2AB	18762	56509;56510;56511	chr2:178590518;178590517;178590516	chr2:179455245;179455244;179455243
N2A	17835	53728;53729;53730	chr2:178590518;178590517;178590516	chr2:179455245;179455244;179455243
N2B	11338	34237;34238;34239	chr2:178590518;178590517;178590516	chr2:179455245;179455244;179455243
Novex-1	11463	34612;34613;34614	chr2:178590518;178590517;178590516	chr2:179455245;179455244;179455243
Novex-2	11530	34813;34814;34815	chr2:178590518;178590517;178590516	chr2:179455245;179455244;179455243
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: Fn3-36
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1894
• 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/T	rs757910559	-2.068	0.978	N	0.765	0.526	0.710765558589	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
I/T	rs757910559	-2.068	0.978	N	0.765	0.526	0.710765558589	gnomAD-4.0.0	1.36898E-06	None	None	None	None	I	None	0	4.47708E-05	None	0	0	None	0	0	0	0	0
I/V	None	None	0.198	N	0.235	0.127	0.407082143382	gnomAD-4.0.0	1.59278E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43419E-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	0.988	likely_pathogenic	0.984	pathogenic	-1.991	Destabilizing	0.983	D	0.678	prob.neutral	None	None	None	None	I
I/C	0.9886	likely_pathogenic	0.9857	pathogenic	-1.061	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
I/D	0.9993	likely_pathogenic	0.9991	pathogenic	-1.509	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	I
I/E	0.9978	likely_pathogenic	0.9971	pathogenic	-1.452	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
I/F	0.9499	likely_pathogenic	0.9366	pathogenic	-1.302	Destabilizing	0.997	D	0.733	prob.delet.	N	0.521903477	None	None	I
I/G	0.9984	likely_pathogenic	0.9979	pathogenic	-2.383	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
I/H	0.9982	likely_pathogenic	0.9974	pathogenic	-1.585	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
I/K	0.9962	likely_pathogenic	0.9943	pathogenic	-1.363	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	I
I/L	0.4512	ambiguous	0.4466	ambiguous	-0.947	Destabilizing	0.798	D	0.449	neutral	N	0.480085879	None	None	I
I/M	0.7655	likely_pathogenic	0.7273	pathogenic	-0.653	Destabilizing	0.997	D	0.705	prob.neutral	D	0.531021737	None	None	I
I/N	0.99	likely_pathogenic	0.9846	pathogenic	-1.218	Destabilizing	0.999	D	0.822	deleterious	D	0.543556585	None	None	I
I/P	0.9876	likely_pathogenic	0.9851	pathogenic	-1.266	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	I
I/Q	0.997	likely_pathogenic	0.9959	pathogenic	-1.34	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
I/R	0.9941	likely_pathogenic	0.9919	pathogenic	-0.792	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
I/S	0.9906	likely_pathogenic	0.9862	pathogenic	-1.882	Destabilizing	0.997	D	0.785	deleterious	D	0.524691861	None	None	I
I/T	0.9826	likely_pathogenic	0.9727	pathogenic	-1.702	Destabilizing	0.978	D	0.765	deleterious	N	0.513335556	None	None	I
I/V	0.1123	likely_benign	0.1035	benign	-1.266	Destabilizing	0.198	N	0.235	neutral	N	0.479696701	None	None	I
I/W	0.999	likely_pathogenic	0.9989	pathogenic	-1.445	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
I/Y	0.9944	likely_pathogenic	0.9922	pathogenic	-1.225	Destabilizing	0.999	D	0.758	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.