TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20386	61381;61382;61383	chr2:178590569;178590568;178590567	chr2:179455296;179455295;179455294
N2AB	18745	56458;56459;56460	chr2:178590569;178590568;178590567	chr2:179455296;179455295;179455294
N2A	17818	53677;53678;53679	chr2:178590569;178590568;178590567	chr2:179455296;179455295;179455294
N2B	11321	34186;34187;34188	chr2:178590569;178590568;178590567	chr2:179455296;179455295;179455294
Novex-1	11446	34561;34562;34563	chr2:178590569;178590568;178590567	chr2:179455296;179455295;179455294
Novex-2	11513	34762;34763;34764	chr2:178590569;178590568;178590567	chr2:179455296;179455295;179455294
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: Fn3-36
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4868
• 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	0.954	N	0.545	0.127	0.332646915603	gnomAD-4.0.0	1.59402E-06	None	None	None	None	N	None	5.67408E-05	0	None	0	0	None	0	0	0	0	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	0.2105	likely_benign	0.2086	benign	-0.596	Destabilizing	0.91	D	0.522	neutral	N	0.463569668	None	None	N
E/C	0.8454	likely_pathogenic	0.8597	pathogenic	-0.024	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/D	0.138	likely_benign	0.1291	benign	-0.631	Destabilizing	0.954	D	0.545	neutral	N	0.384895454	None	None	N
E/F	0.795	likely_pathogenic	0.7984	pathogenic	-0.555	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
E/G	0.2198	likely_benign	0.2101	benign	-0.838	Destabilizing	0.98	D	0.509	neutral	N	0.436287067	None	None	N
E/H	0.5357	ambiguous	0.5253	ambiguous	-0.683	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
E/I	0.5132	ambiguous	0.5084	ambiguous	0.021	Stabilizing	0.991	D	0.607	neutral	None	None	None	None	N
E/K	0.2637	likely_benign	0.244	benign	0.055	Stabilizing	0.961	D	0.547	neutral	N	0.450928445	None	None	N
E/L	0.5172	ambiguous	0.515	ambiguous	0.021	Stabilizing	0.97	D	0.54	neutral	None	None	None	None	N
E/M	0.5255	ambiguous	0.5394	ambiguous	0.378	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	N
E/N	0.2523	likely_benign	0.2507	benign	-0.223	Destabilizing	0.985	D	0.493	neutral	None	None	None	None	N
E/P	0.9633	likely_pathogenic	0.9438	pathogenic	-0.164	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	N
E/Q	0.1805	likely_benign	0.1777	benign	-0.194	Destabilizing	0.993	D	0.506	neutral	N	0.45387275	None	None	N
E/R	0.4331	ambiguous	0.3959	ambiguous	0.148	Stabilizing	0.996	D	0.47	neutral	None	None	None	None	N
E/S	0.2206	likely_benign	0.2249	benign	-0.421	Destabilizing	0.942	D	0.53	neutral	None	None	None	None	N
E/T	0.2014	likely_benign	0.2081	benign	-0.229	Destabilizing	0.155	N	0.197	neutral	None	None	None	None	N
E/V	0.3041	likely_benign	0.3002	benign	-0.164	Destabilizing	0.961	D	0.501	neutral	N	0.515998644	None	None	N
E/W	0.9229	likely_pathogenic	0.9166	pathogenic	-0.414	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/Y	0.6525	likely_pathogenic	0.6429	pathogenic	-0.316	Destabilizing	0.999	D	0.578	neutral	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.