TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2096	6511;6512;6513	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303
N2AB	2096	6511;6512;6513	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303
N2A	2096	6511;6512;6513	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303
N2B	2050	6373;6374;6375	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303
Novex-1	2050	6373;6374;6375	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303
Novex-2	2050	6373;6374;6375	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303
Novex-3	2096	6511;6512;6513	chr2:178775578;178775577;178775576	chr2:179640305;179640304;179640303

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-10
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3356
• 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
H/R	None	None	0.031	N	0.323	0.244	0.212008924253	gnomAD-4.0.0	1.59062E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85659E-06	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
H/A	0.7027	likely_pathogenic	0.6732	pathogenic	-0.322	Destabilizing	0.97	D	0.618	neutral	None	None	None	None	N
H/C	0.4304	ambiguous	0.4221	ambiguous	0.531	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
H/D	0.7836	likely_pathogenic	0.7529	pathogenic	-0.47	Destabilizing	0.994	D	0.654	neutral	N	0.500503332	None	None	N
H/E	0.7396	likely_pathogenic	0.7101	pathogenic	-0.38	Destabilizing	0.97	D	0.566	neutral	None	None	None	None	N
H/F	0.6462	likely_pathogenic	0.6074	pathogenic	0.886	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
H/G	0.8061	likely_pathogenic	0.7766	pathogenic	-0.69	Destabilizing	0.985	D	0.635	neutral	None	None	None	None	N
H/I	0.6446	likely_pathogenic	0.6132	pathogenic	0.686	Stabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
H/K	0.4597	ambiguous	0.4318	ambiguous	-0.235	Destabilizing	0.942	D	0.593	neutral	None	None	None	None	N
H/L	0.3187	likely_benign	0.2874	benign	0.686	Stabilizing	0.961	D	0.671	neutral	N	0.466850524	None	None	N
H/M	0.808	likely_pathogenic	0.7818	pathogenic	0.499	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
H/N	0.3034	likely_benign	0.278	benign	-0.308	Destabilizing	0.98	D	0.572	neutral	N	0.495956623	None	None	N
H/P	0.837	likely_pathogenic	0.8109	pathogenic	0.372	Stabilizing	0.998	D	0.711	prob.delet.	D	0.538691185	None	None	N
H/Q	0.4081	ambiguous	0.403	ambiguous	-0.064	Destabilizing	0.989	D	0.593	neutral	N	0.458389956	None	None	N
H/R	0.1487	likely_benign	0.1465	benign	-0.967	Destabilizing	0.031	N	0.323	neutral	N	0.341734738	None	None	N
H/S	0.5684	likely_pathogenic	0.5331	ambiguous	-0.175	Destabilizing	0.985	D	0.601	neutral	None	None	None	None	N
H/T	0.598	likely_pathogenic	0.565	pathogenic	0.018	Stabilizing	0.996	D	0.675	neutral	None	None	None	None	N
H/V	0.5502	ambiguous	0.5133	ambiguous	0.372	Stabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
H/W	0.7103	likely_pathogenic	0.6773	pathogenic	1.072	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
H/Y	0.2637	likely_benign	0.2337	benign	1.175	Stabilizing	0.998	D	0.601	neutral	N	0.503918272	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.