TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26848	80767;80768;80769	chr2:178565590;178565589;178565588	chr2:179430317;179430316;179430315
N2AB	25207	75844;75845;75846	chr2:178565590;178565589;178565588	chr2:179430317;179430316;179430315
N2A	24280	73063;73064;73065	chr2:178565590;178565589;178565588	chr2:179430317;179430316;179430315
N2B	17783	53572;53573;53574	chr2:178565590;178565589;178565588	chr2:179430317;179430316;179430315
Novex-1	17908	53947;53948;53949	chr2:178565590;178565589;178565588	chr2:179430317;179430316;179430315
Novex-2	17975	54148;54149;54150	chr2:178565590;178565589;178565588	chr2:179430317;179430316;179430315
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: Fn3-83
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.357
• 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/Q	rs898433512	None	0.991	N	0.615	0.319	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs898433512	None	0.991	N	0.615	0.319	None	gnomAD-4.0.0	1.31494E-05	None	None	None	None	N	None	4.82556E-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	0.2626	likely_benign	0.2838	benign	-0.82	Destabilizing	0.861	D	0.555	neutral	N	0.467965424	None	None	N
E/C	0.9316	likely_pathogenic	0.9393	pathogenic	-0.577	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/D	0.3969	ambiguous	0.4247	ambiguous	-1.135	Destabilizing	0.005	N	0.297	neutral	N	0.469927207	None	None	N
E/F	0.9197	likely_pathogenic	0.9281	pathogenic	-0.052	Destabilizing	0.995	D	0.79	deleterious	None	None	None	None	N
E/G	0.4622	ambiguous	0.4813	ambiguous	-1.225	Destabilizing	0.976	D	0.663	neutral	N	0.487159316	None	None	N
E/H	0.8022	likely_pathogenic	0.8222	pathogenic	-0.413	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/I	0.4772	ambiguous	0.5114	ambiguous	0.302	Stabilizing	0.98	D	0.803	deleterious	None	None	None	None	N
E/K	0.4761	ambiguous	0.4991	ambiguous	-0.964	Destabilizing	0.958	D	0.504	neutral	N	0.471823792	None	None	N
E/L	0.6455	likely_pathogenic	0.6756	pathogenic	0.302	Stabilizing	0.962	D	0.738	prob.delet.	None	None	None	None	N
E/M	0.5984	likely_pathogenic	0.6345	pathogenic	0.728	Stabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
E/N	0.5828	likely_pathogenic	0.6047	pathogenic	-1.411	Destabilizing	0.959	D	0.621	neutral	None	None	None	None	N
E/P	0.7536	likely_pathogenic	0.803	pathogenic	-0.051	Destabilizing	0.938	D	0.763	deleterious	None	None	None	None	N
E/Q	0.273	likely_benign	0.2909	benign	-1.217	Destabilizing	0.991	D	0.615	neutral	N	0.489756192	None	None	N
E/R	0.6452	likely_pathogenic	0.6739	pathogenic	-0.643	Destabilizing	0.991	D	0.659	neutral	None	None	None	None	N
E/S	0.4118	ambiguous	0.4498	ambiguous	-1.784	Destabilizing	0.891	D	0.475	neutral	None	None	None	None	N
E/T	0.3535	ambiguous	0.3947	ambiguous	-1.449	Destabilizing	0.141	N	0.375	neutral	None	None	None	None	N
E/V	0.2972	likely_benign	0.3237	benign	-0.051	Destabilizing	0.93	D	0.703	prob.neutral	N	0.473916906	None	None	N
E/W	0.9742	likely_pathogenic	0.9743	pathogenic	0.175	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.8518	likely_pathogenic	0.8596	pathogenic	0.172	Stabilizing	0.999	D	0.781	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.