TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21939	66040;66041;66042	chr2:178582988;178582987;178582986	chr2:179447715;179447714;179447713
N2AB	20298	61117;61118;61119	chr2:178582988;178582987;178582986	chr2:179447715;179447714;179447713
N2A	19371	58336;58337;58338	chr2:178582988;178582987;178582986	chr2:179447715;179447714;179447713
N2B	12874	38845;38846;38847	chr2:178582988;178582987;178582986	chr2:179447715;179447714;179447713
Novex-1	12999	39220;39221;39222	chr2:178582988;178582987;178582986	chr2:179447715;179447714;179447713
Novex-2	13066	39421;39422;39423	chr2:178582988;178582987;178582986	chr2:179447715;179447714;179447713
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-125
• Domain position: 74
• Structural Position: 159
• Q(SASA): 0.4856
• 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	None	None	0.989	N	0.615	0.38	0.393623145366	gnomAD-4.0.0	7.12946E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.26219E-07	0	0
E/Q	None	None	0.998	N	0.645	0.226	0.496957384516	gnomAD-4.0.0	7.12946E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.26219E-07	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	0.1542	likely_benign	0.1629	benign	-0.233	Destabilizing	0.978	D	0.587	neutral	N	0.491596924	None	None	N
E/C	0.8033	likely_pathogenic	0.805	pathogenic	0.423	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.2038	likely_benign	0.2351	benign	-0.34	Destabilizing	0.217	N	0.229	neutral	D	0.523535984	None	None	N
E/F	0.7759	likely_pathogenic	0.7803	pathogenic	-0.615	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/G	0.2324	likely_benign	0.2504	benign	-0.407	Destabilizing	0.989	D	0.691	prob.neutral	D	0.529981954	None	None	N
E/H	0.4253	ambiguous	0.4303	ambiguous	-0.795	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.3224	likely_benign	0.3142	benign	0.177	Stabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
E/K	0.129	likely_benign	0.1265	benign	0.522	Stabilizing	0.989	D	0.615	neutral	N	0.478358268	None	None	N
E/L	0.4469	ambiguous	0.4425	ambiguous	0.177	Stabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/M	0.4264	ambiguous	0.4203	ambiguous	0.569	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/N	0.2778	likely_benign	0.3055	benign	0.393	Stabilizing	0.992	D	0.661	neutral	None	None	None	None	N
E/P	0.9848	likely_pathogenic	0.9867	pathogenic	0.06	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/Q	0.1018	likely_benign	0.1008	benign	0.387	Stabilizing	0.998	D	0.645	neutral	N	0.508201172	None	None	N
E/R	0.2408	likely_benign	0.234	benign	0.362	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
E/S	0.17	likely_benign	0.1853	benign	0.244	Stabilizing	0.82	D	0.315	neutral	None	None	None	None	N
E/T	0.1533	likely_benign	0.1555	benign	0.383	Stabilizing	0.983	D	0.653	neutral	None	None	None	None	N
E/V	0.1822	likely_benign	0.172	benign	0.06	Stabilizing	0.998	D	0.716	prob.delet.	N	0.503699429	None	None	N
E/W	0.9118	likely_pathogenic	0.9141	pathogenic	-0.645	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/Y	0.6808	likely_pathogenic	0.6889	pathogenic	-0.402	Destabilizing	1.0	D	0.767	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.