TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2902	8929;8930;8931	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602
N2AB	2902	8929;8930;8931	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602
N2A	2902	8929;8930;8931	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602
N2B	2856	8791;8792;8793	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602
Novex-1	2856	8791;8792;8793	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602
Novex-2	2856	8791;8792;8793	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602
Novex-3	2902	8929;8930;8931	chr2:178769877;178769876;178769875	chr2:179634604;179634603;179634602

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-19
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2737
• 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/A	rs2091213467	None	0.977	D	0.62	0.641	0.605955498237	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/A	rs2091213467	None	0.977	D	0.62	0.641	0.605955498237	gnomAD-4.0.0	3.84183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.17525E-06	0	0
E/G	None	None	0.993	D	0.737	0.706	0.705062143596	gnomAD-4.0.0	1.59053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85651E-06	0	0
E/Q	rs143767300	-0.962	0.568	N	0.296	0.247	None	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	1.23062E-04	0	None	0	0	None	0	None	0	0	0
E/Q	rs143767300	-0.962	0.568	N	0.296	0.247	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs143767300	-0.962	0.568	N	0.296	0.247	None	gnomAD-4.0.0	2.5613E-06	None	None	None	None	N	None	3.38341E-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	0.3219	likely_benign	0.319	benign	-0.804	Destabilizing	0.977	D	0.62	neutral	D	0.641585319	None	None	N
E/C	0.9572	likely_pathogenic	0.9576	pathogenic	-0.434	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/D	0.5331	ambiguous	0.4617	ambiguous	-1.154	Destabilizing	0.977	D	0.477	neutral	D	0.533216831	None	None	N
E/F	0.9396	likely_pathogenic	0.9366	pathogenic	-0.372	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/G	0.5818	likely_pathogenic	0.5819	pathogenic	-1.155	Destabilizing	0.993	D	0.737	prob.delet.	D	0.661266666	None	None	N
E/H	0.8011	likely_pathogenic	0.812	pathogenic	-0.659	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.6169	likely_pathogenic	0.5934	pathogenic	0.144	Stabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
E/K	0.4849	ambiguous	0.513	ambiguous	-0.566	Destabilizing	0.955	D	0.519	neutral	N	0.504986905	None	None	N
E/L	0.7454	likely_pathogenic	0.7315	pathogenic	0.144	Stabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
E/M	0.7148	likely_pathogenic	0.7106	pathogenic	0.564	Stabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
E/N	0.663	likely_pathogenic	0.6382	pathogenic	-0.979	Destabilizing	0.995	D	0.687	prob.neutral	None	None	None	None	N
E/P	0.9858	likely_pathogenic	0.9846	pathogenic	-0.15	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
E/Q	0.2092	likely_benign	0.2375	benign	-0.875	Destabilizing	0.568	D	0.296	neutral	N	0.506569646	None	None	N
E/R	0.6345	likely_pathogenic	0.6793	pathogenic	-0.317	Destabilizing	0.99	D	0.689	prob.neutral	None	None	None	None	N
E/S	0.402	ambiguous	0.3803	ambiguous	-1.287	Destabilizing	0.983	D	0.583	neutral	None	None	None	None	N
E/T	0.393	ambiguous	0.3898	ambiguous	-1.001	Destabilizing	0.995	D	0.758	deleterious	None	None	None	None	N
E/V	0.4057	ambiguous	0.3905	ambiguous	-0.15	Destabilizing	0.997	D	0.774	deleterious	D	0.604457417	None	None	N
E/W	0.9877	likely_pathogenic	0.9878	pathogenic	-0.159	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/Y	0.9166	likely_pathogenic	0.9147	pathogenic	-0.125	Destabilizing	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.