TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35356	106291;106292;106293	chr2:178530549;178530548;178530547	chr2:179395276;179395275;179395274
N2AB	33715	101368;101369;101370	chr2:178530549;178530548;178530547	chr2:179395276;179395275;179395274
N2A	32788	98587;98588;98589	chr2:178530549;178530548;178530547	chr2:179395276;179395275;179395274
N2B	26291	79096;79097;79098	chr2:178530549;178530548;178530547	chr2:179395276;179395275;179395274
Novex-1	26416	79471;79472;79473	chr2:178530549;178530548;178530547	chr2:179395276;179395275;179395274
Novex-2	26483	79672;79673;79674	chr2:178530549;178530548;178530547	chr2:179395276;179395275;179395274
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: Ig-165
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.4211
• 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/D	None	None	0.014	N	0.371	0.054	0.269111216191	gnomAD-4.0.0	1.36828E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79879E-06	0	0
E/K	rs886055218	-0.304	0.058	N	0.39	0.201	0.272205846399	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/K	rs886055218	-0.304	0.058	N	0.39	0.201	0.272205846399	gnomAD-4.0.0	1.36829E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99397E-07	0	1.6564E-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	0.2139	likely_benign	0.1894	benign	-0.791	Destabilizing	0.822	D	0.595	neutral	D	0.533982264	None	None	N
E/C	0.8852	likely_pathogenic	0.8618	pathogenic	-0.456	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
E/D	0.1837	likely_benign	0.1545	benign	-1.267	Destabilizing	0.014	N	0.371	neutral	N	0.511972196	None	None	N
E/F	0.7779	likely_pathogenic	0.7239	pathogenic	-0.479	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
E/G	0.2888	likely_benign	0.2361	benign	-1.163	Destabilizing	0.822	D	0.67	neutral	N	0.499837473	None	None	N
E/H	0.5748	likely_pathogenic	0.5053	ambiguous	-0.931	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
E/I	0.374	ambiguous	0.3221	benign	0.225	Stabilizing	0.978	D	0.786	deleterious	None	None	None	None	N
E/K	0.1804	likely_benign	0.1473	benign	-0.818	Destabilizing	0.058	N	0.39	neutral	N	0.501272413	None	None	N
E/L	0.4855	ambiguous	0.4248	ambiguous	0.225	Stabilizing	0.978	D	0.77	deleterious	None	None	None	None	N
E/M	0.4805	ambiguous	0.4364	ambiguous	0.759	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/N	0.2673	likely_benign	0.2211	benign	-1.172	Destabilizing	0.915	D	0.637	neutral	None	None	None	None	N
E/P	0.8907	likely_pathogenic	0.8569	pathogenic	-0.092	Destabilizing	0.978	D	0.759	deleterious	None	None	None	None	N
E/Q	0.1853	likely_benign	0.1585	benign	-1.018	Destabilizing	0.942	D	0.595	neutral	N	0.514953786	None	None	N
E/R	0.3398	likely_benign	0.2852	benign	-0.667	Destabilizing	0.915	D	0.632	neutral	None	None	None	None	N
E/S	0.2508	likely_benign	0.2115	benign	-1.527	Destabilizing	0.754	D	0.533	neutral	None	None	None	None	N
E/T	0.24	likely_benign	0.2068	benign	-1.221	Destabilizing	0.956	D	0.709	prob.delet.	None	None	None	None	N
E/V	0.2597	likely_benign	0.2284	benign	-0.092	Destabilizing	0.971	D	0.758	deleterious	N	0.479918493	None	None	N
E/W	0.916	likely_pathogenic	0.8867	pathogenic	-0.373	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
E/Y	0.7049	likely_pathogenic	0.6326	pathogenic	-0.272	Destabilizing	0.993	D	0.763	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.