TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24420	73483;73484;73485	chr2:178572874;178572873;178572872	chr2:179437601;179437600;179437599
N2AB	22779	68560;68561;68562	chr2:178572874;178572873;178572872	chr2:179437601;179437600;179437599
N2A	21852	65779;65780;65781	chr2:178572874;178572873;178572872	chr2:179437601;179437600;179437599
N2B	15355	46288;46289;46290	chr2:178572874;178572873;178572872	chr2:179437601;179437600;179437599
Novex-1	15480	46663;46664;46665	chr2:178572874;178572873;178572872	chr2:179437601;179437600;179437599
Novex-2	15547	46864;46865;46866	chr2:178572874;178572873;178572872	chr2:179437601;179437600;179437599
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: Fn3-65
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.3263
• 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
E/K	rs1265445775	None	0.032	N	0.265	0.324	0.243398259712	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1265445775	None	0.032	N	0.265	0.324	0.243398259712	gnomAD-4.0.0	7.69014E-06	None	None	None	None	N	None	3.38284E-05	0	None	0	0	None	0	0	0	0	1.13837E-04

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	0.1568	likely_benign	0.1589	benign	-0.397	Destabilizing	0.841	D	0.448	neutral	N	0.450227517	None	None	N
E/C	0.7864	likely_pathogenic	0.8057	pathogenic	-0.005	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
E/D	0.3551	ambiguous	0.354	ambiguous	-0.887	Destabilizing	0.914	D	0.37	neutral	N	0.480929389	None	None	N
E/F	0.8355	likely_pathogenic	0.8335	pathogenic	-0.642	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
E/G	0.2502	likely_benign	0.2526	benign	-0.653	Destabilizing	0.974	D	0.548	neutral	D	0.526784146	None	None	N
E/H	0.6077	likely_pathogenic	0.6024	pathogenic	-0.962	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	N
E/I	0.3251	likely_benign	0.3181	benign	0.258	Stabilizing	0.99	D	0.784	deleterious	None	None	None	None	N
E/K	0.1605	likely_benign	0.1499	benign	-0.164	Destabilizing	0.032	N	0.265	neutral	N	0.425155714	None	None	N
E/L	0.4607	ambiguous	0.4512	ambiguous	0.258	Stabilizing	0.98	D	0.675	prob.neutral	None	None	None	None	N
E/M	0.4212	ambiguous	0.4153	ambiguous	0.694	Stabilizing	0.999	D	0.739	deleterious	None	None	None	None	N
E/N	0.4793	ambiguous	0.4858	ambiguous	-0.355	Destabilizing	0.98	D	0.573	neutral	None	None	None	None	N
E/P	0.9704	likely_pathogenic	0.9672	pathogenic	0.062	Stabilizing	0.99	D	0.646	neutral	None	None	None	None	N
E/Q	0.1267	likely_benign	0.1248	benign	-0.318	Destabilizing	0.914	D	0.553	neutral	N	0.512353411	None	None	N
E/R	0.2824	likely_benign	0.2706	benign	-0.176	Destabilizing	0.961	D	0.602	neutral	None	None	None	None	N
E/S	0.2441	likely_benign	0.2571	benign	-0.578	Destabilizing	0.933	D	0.501	neutral	None	None	None	None	N
E/T	0.2106	likely_benign	0.2104	benign	-0.379	Destabilizing	0.98	D	0.567	neutral	None	None	None	None	N
E/V	0.1706	likely_benign	0.1692	benign	0.062	Stabilizing	0.974	D	0.678	prob.neutral	N	0.497250673	None	None	N
E/W	0.949	likely_pathogenic	0.9473	pathogenic	-0.673	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
E/Y	0.7848	likely_pathogenic	0.7887	pathogenic	-0.45	Destabilizing	0.997	D	0.753	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.