TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32290	97093;97094;97095	chr2:178543105;178543104;178543103	chr2:179407832;179407831;179407830
N2AB	30649	92170;92171;92172	chr2:178543105;178543104;178543103	chr2:179407832;179407831;179407830
N2A	29722	89389;89390;89391	chr2:178543105;178543104;178543103	chr2:179407832;179407831;179407830
N2B	23225	69898;69899;69900	chr2:178543105;178543104;178543103	chr2:179407832;179407831;179407830
Novex-1	23350	70273;70274;70275	chr2:178543105;178543104;178543103	chr2:179407832;179407831;179407830
Novex-2	23417	70474;70475;70476	chr2:178543105;178543104;178543103	chr2:179407832;179407831;179407830
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-123
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.5228
• 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/K	rs1060500512	None	0.953	N	0.535	0.285	0.383921772103	gnomAD-4.0.0	1.37408E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80613E-06	0	0
E/Q	None	None	0.976	N	0.621	0.174	0.259272394797	gnomAD-4.0.0	6.87038E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16393E-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
E/A	0.3151	likely_benign	0.3063	benign	-0.621	Destabilizing	0.976	D	0.579	neutral	N	0.511822188	None	None	I
E/C	0.9295	likely_pathogenic	0.9259	pathogenic	-0.364	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
E/D	0.216	likely_benign	0.1917	benign	-1.025	Destabilizing	0.026	N	0.16	neutral	N	0.483403436	None	None	I
E/F	0.8986	likely_pathogenic	0.891	pathogenic	0.249	Stabilizing	0.998	D	0.813	deleterious	None	None	None	None	I
E/G	0.3336	likely_benign	0.3289	benign	-1.036	Destabilizing	0.953	D	0.609	neutral	N	0.490091696	None	None	I
E/H	0.7479	likely_pathogenic	0.7431	pathogenic	0.061	Stabilizing	0.998	D	0.601	neutral	None	None	None	None	I
E/I	0.6011	likely_pathogenic	0.5742	pathogenic	0.527	Stabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
E/K	0.3892	ambiguous	0.3868	ambiguous	-0.521	Destabilizing	0.953	D	0.535	neutral	N	0.471987441	None	None	I
E/L	0.6111	likely_pathogenic	0.5891	pathogenic	0.527	Stabilizing	0.995	D	0.74	deleterious	None	None	None	None	I
E/M	0.6257	likely_pathogenic	0.6099	pathogenic	0.894	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
E/N	0.4894	ambiguous	0.458	ambiguous	-1.149	Destabilizing	0.964	D	0.6	neutral	None	None	None	None	I
E/P	0.7191	likely_pathogenic	0.6933	pathogenic	0.166	Stabilizing	0.998	D	0.632	neutral	None	None	None	None	I
E/Q	0.2373	likely_benign	0.2369	benign	-0.947	Destabilizing	0.976	D	0.621	neutral	N	0.475189384	None	None	I
E/R	0.5703	likely_pathogenic	0.5756	pathogenic	-0.164	Destabilizing	0.995	D	0.572	neutral	None	None	None	None	I
E/S	0.3948	ambiguous	0.3871	ambiguous	-1.493	Destabilizing	0.964	D	0.501	neutral	None	None	None	None	I
E/T	0.4276	ambiguous	0.4237	ambiguous	-1.136	Destabilizing	0.982	D	0.663	prob.neutral	None	None	None	None	I
E/V	0.3581	ambiguous	0.3419	ambiguous	0.166	Stabilizing	0.998	D	0.598	neutral	N	0.502530701	None	None	I
E/W	0.9647	likely_pathogenic	0.9631	pathogenic	0.529	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
E/Y	0.831	likely_pathogenic	0.8193	pathogenic	0.525	Stabilizing	0.998	D	0.827	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.