TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33611	101056;101057;101058	chr2:178535784;178535783;178535782	chr2:179400511;179400510;179400509
N2AB	31970	96133;96134;96135	chr2:178535784;178535783;178535782	chr2:179400511;179400510;179400509
N2A	31043	93352;93353;93354	chr2:178535784;178535783;178535782	chr2:179400511;179400510;179400509
N2B	24546	73861;73862;73863	chr2:178535784;178535783;178535782	chr2:179400511;179400510;179400509
Novex-1	24671	74236;74237;74238	chr2:178535784;178535783;178535782	chr2:179400511;179400510;179400509
Novex-2	24738	74437;74438;74439	chr2:178535784;178535783;178535782	chr2:179400511;179400510;179400509
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-159
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2104
• 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	rs769704328	-0.271	0.992	N	0.593	0.255	0.231873229951	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/V	rs2154136906	None	0.994	N	0.707	0.447	0.303781844768	gnomAD-4.0.0	1.59318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.6656	likely_pathogenic	0.4978	ambiguous	-0.667	Destabilizing	0.965	D	0.532	neutral	N	0.503138416	None	None	N
E/C	0.9899	likely_pathogenic	0.9727	pathogenic	-0.209	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
E/D	0.2919	likely_benign	0.2125	benign	-0.547	Destabilizing	0.002	N	0.183	neutral	N	0.441183093	None	None	N
E/F	0.9909	likely_pathogenic	0.9719	pathogenic	-0.243	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/G	0.7091	likely_pathogenic	0.5335	ambiguous	-0.937	Destabilizing	0.989	D	0.559	neutral	N	0.463849309	None	None	N
E/H	0.9408	likely_pathogenic	0.8556	pathogenic	-0.132	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
E/I	0.9602	likely_pathogenic	0.9061	pathogenic	0.039	Stabilizing	0.997	D	0.795	deleterious	None	None	None	None	N
E/K	0.7142	likely_pathogenic	0.5131	ambiguous	0.155	Stabilizing	0.981	D	0.482	neutral	N	0.481800352	None	None	N
E/L	0.961	likely_pathogenic	0.8998	pathogenic	0.039	Stabilizing	0.997	D	0.762	deleterious	None	None	None	None	N
E/M	0.9322	likely_pathogenic	0.8536	pathogenic	0.239	Stabilizing	0.996	D	0.724	prob.delet.	None	None	None	None	N
E/N	0.7081	likely_pathogenic	0.5187	ambiguous	-0.415	Destabilizing	0.962	D	0.601	neutral	None	None	None	None	N
E/P	0.9972	likely_pathogenic	0.9926	pathogenic	-0.176	Destabilizing	0.98	D	0.657	neutral	None	None	None	None	N
E/Q	0.5072	ambiguous	0.3522	ambiguous	-0.331	Destabilizing	0.992	D	0.593	neutral	N	0.481280277	None	None	N
E/R	0.8599	likely_pathogenic	0.7122	pathogenic	0.421	Stabilizing	0.996	D	0.645	neutral	None	None	None	None	N
E/S	0.6803	likely_pathogenic	0.4843	ambiguous	-0.585	Destabilizing	0.947	D	0.491	neutral	None	None	None	None	N
E/T	0.803	likely_pathogenic	0.644	pathogenic	-0.353	Destabilizing	0.994	D	0.606	neutral	None	None	None	None	N
E/V	0.8651	likely_pathogenic	0.7527	pathogenic	-0.176	Destabilizing	0.994	D	0.707	prob.neutral	N	0.46842168	None	None	N
E/W	0.9976	likely_pathogenic	0.992	pathogenic	0.036	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/Y	0.9791	likely_pathogenic	0.9428	pathogenic	0.034	Stabilizing	1.0	D	0.735	prob.delet.	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.