TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19765	59518;59519;59520	chr2:178592826;178592825;178592824	chr2:179457553;179457552;179457551
N2AB	18124	54595;54596;54597	chr2:178592826;178592825;178592824	chr2:179457553;179457552;179457551
N2A	17197	51814;51815;51816	chr2:178592826;178592825;178592824	chr2:179457553;179457552;179457551
N2B	10700	32323;32324;32325	chr2:178592826;178592825;178592824	chr2:179457553;179457552;179457551
Novex-1	10825	32698;32699;32700	chr2:178592826;178592825;178592824	chr2:179457553;179457552;179457551
Novex-2	10892	32899;32900;32901	chr2:178592826;178592825;178592824	chr2:179457553;179457552;179457551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-31
• Domain position: 86
• Structural Position: 117
• Q(SASA): 0.5273
• 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
E/V	rs766141647	-0.131	1.0	N	0.819	0.429	0.557481709393	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	1.65837E-04
E/V	rs766141647	-0.131	1.0	N	0.819	0.429	0.557481709393	gnomAD-4.0.0	8.21192E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	8.11707E-05	8.28555E-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
E/A	0.154	likely_benign	0.1308	benign	-0.84	Destabilizing	0.999	D	0.736	prob.delet.	N	0.460353218	None	None	I
E/C	0.7928	likely_pathogenic	0.7407	pathogenic	-0.288	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
E/D	0.2846	likely_benign	0.2399	benign	-0.697	Destabilizing	0.999	D	0.615	neutral	N	0.489251973	None	None	I
E/F	0.6617	likely_pathogenic	0.6146	pathogenic	-0.301	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/G	0.2941	likely_benign	0.2322	benign	-1.143	Destabilizing	1.0	D	0.779	deleterious	N	0.492596457	None	None	I
E/H	0.5772	likely_pathogenic	0.4922	ambiguous	-0.3	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
E/I	0.211	likely_benign	0.1881	benign	-0.03	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
E/K	0.1663	likely_benign	0.1344	benign	-0.015	Destabilizing	0.999	D	0.733	prob.delet.	N	0.453061886	None	None	I
E/L	0.3345	likely_benign	0.304	benign	-0.03	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/M	0.3656	ambiguous	0.327	benign	0.307	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
E/N	0.4123	ambiguous	0.3414	ambiguous	-0.608	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
E/P	0.3725	ambiguous	0.3264	benign	-0.279	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/Q	0.1568	likely_benign	0.1362	benign	-0.517	Destabilizing	1.0	D	0.73	prob.delet.	N	0.449290862	None	None	I
E/R	0.3192	likely_benign	0.2548	benign	0.264	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
E/S	0.282	likely_benign	0.2395	benign	-0.829	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
E/T	0.23	likely_benign	0.2086	benign	-0.564	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/V	0.1387	likely_benign	0.1244	benign	-0.279	Destabilizing	1.0	D	0.819	deleterious	N	0.424277775	None	None	I
E/W	0.9144	likely_pathogenic	0.8752	pathogenic	0.037	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/Y	0.6016	likely_pathogenic	0.5308	ambiguous	-0.006	Destabilizing	1.0	D	0.81	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.