TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18138	54637;54638;54639	chr2:178604275;178604274;178604273	chr2:179469002;179469001;179469000
N2AB	16497	49714;49715;49716	chr2:178604275;178604274;178604273	chr2:179469002;179469001;179469000
N2A	15570	46933;46934;46935	chr2:178604275;178604274;178604273	chr2:179469002;179469001;179469000
N2B	9073	27442;27443;27444	chr2:178604275;178604274;178604273	chr2:179469002;179469001;179469000
Novex-1	9198	27817;27818;27819	chr2:178604275;178604274;178604273	chr2:179469002;179469001;179469000
Novex-2	9265	28018;28019;28020	chr2:178604275;178604274;178604273	chr2:179469002;179469001;179469000
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: Fn3-19
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.1225
• 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	0.425	N	0.515	0.081	0.275641507738	gnomAD-4.0.0	1.82077E-06	None	None	None	None	N	None	0	0	None	0	2.86812E-05	None	0	0	0	0	0
E/Q	None	None	0.01	N	0.254	0.148	0.192905019026	gnomAD-4.0.0	1.86926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.29746E-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
E/A	0.4449	ambiguous	0.4101	ambiguous	-0.758	Destabilizing	0.425	N	0.515	neutral	N	0.475981605	None	None	N
E/C	0.8844	likely_pathogenic	0.8868	pathogenic	-0.323	Destabilizing	0.995	D	0.607	neutral	None	None	None	None	N
E/D	0.6346	likely_pathogenic	0.6809	pathogenic	-1.728	Destabilizing	0.425	N	0.515	neutral	N	0.489700264	None	None	N
E/F	0.8789	likely_pathogenic	0.9029	pathogenic	-0.199	Destabilizing	0.893	D	0.611	neutral	None	None	None	None	N
E/G	0.7197	likely_pathogenic	0.7396	pathogenic	-1.233	Destabilizing	0.642	D	0.613	neutral	D	0.527045144	None	None	N
E/H	0.7997	likely_pathogenic	0.8321	pathogenic	-0.362	Destabilizing	0.944	D	0.585	neutral	None	None	None	None	N
E/I	0.4417	ambiguous	0.394	ambiguous	0.59	Stabilizing	0.031	N	0.553	neutral	None	None	None	None	N
E/K	0.6156	likely_pathogenic	0.6227	pathogenic	-0.87	Destabilizing	0.01	N	0.245	neutral	N	0.405081512	None	None	N
E/L	0.6487	likely_pathogenic	0.6256	pathogenic	0.59	Stabilizing	0.003	N	0.575	neutral	None	None	None	None	N
E/M	0.6172	likely_pathogenic	0.5866	pathogenic	1.248	Stabilizing	0.893	D	0.551	neutral	None	None	None	None	N
E/N	0.7711	likely_pathogenic	0.8005	pathogenic	-1.419	Destabilizing	0.704	D	0.572	neutral	None	None	None	None	N
E/P	0.995	likely_pathogenic	0.996	pathogenic	0.16	Stabilizing	0.828	D	0.605	neutral	None	None	None	None	N
E/Q	0.2185	likely_benign	0.208	benign	-1.065	Destabilizing	0.01	N	0.254	neutral	N	0.404446794	None	None	N
E/R	0.6925	likely_pathogenic	0.7095	pathogenic	-0.792	Destabilizing	0.329	N	0.547	neutral	None	None	None	None	N
E/S	0.5405	ambiguous	0.5477	ambiguous	-1.983	Destabilizing	0.495	N	0.531	neutral	None	None	None	None	N
E/T	0.5296	ambiguous	0.4917	ambiguous	-1.535	Destabilizing	0.495	N	0.598	neutral	None	None	None	None	N
E/V	0.3487	ambiguous	0.3115	benign	0.16	Stabilizing	0.27	N	0.568	neutral	N	0.459934717	None	None	N
E/W	0.971	likely_pathogenic	0.977	pathogenic	-0.244	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
E/Y	0.8327	likely_pathogenic	0.8677	pathogenic	0.033	Stabilizing	0.981	D	0.589	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.