TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13707	41344;41345;41346	chr2:178636608;178636607;178636606	chr2:179501335;179501334;179501333
N2AB	12066	36421;36422;36423	chr2:178636608;178636607;178636606	chr2:179501335;179501334;179501333
N2A	11139	33640;33641;33642	chr2:178636608;178636607;178636606	chr2:179501335;179501334;179501333
N2B	4642	14149;14150;14151	chr2:178636608;178636607;178636606	chr2:179501335;179501334;179501333
Novex-1	4767	14524;14525;14526	chr2:178636608;178636607;178636606	chr2:179501335;179501334;179501333
Novex-2	4834	14725;14726;14727	chr2:178636608;178636607;178636606	chr2:179501335;179501334;179501333
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-87
• Domain position: 24
• Structural Position: 31
• Q(SASA): 0.4902
• 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/G	None	None	0.993	D	0.749	0.659	0.711402520684	gnomAD-4.0.0	2.05305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69881E-06	0	0
E/Q	rs1173154586	-0.795	0.997	N	0.687	0.336	0.411401001288	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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	0.7674	likely_pathogenic	0.839	pathogenic	-0.73	Destabilizing	0.977	D	0.665	neutral	D	0.597337859	None	None	N
E/C	0.9951	likely_pathogenic	0.9963	pathogenic	-0.558	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/D	0.5631	ambiguous	0.628	pathogenic	-1.397	Destabilizing	0.117	N	0.273	neutral	N	0.512697036	None	None	N
E/F	0.9953	likely_pathogenic	0.9962	pathogenic	-0.028	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/G	0.8488	likely_pathogenic	0.9055	pathogenic	-1.158	Destabilizing	0.993	D	0.749	deleterious	D	0.613766662	None	None	N
E/H	0.95	likely_pathogenic	0.9623	pathogenic	-0.469	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/I	0.9635	likely_pathogenic	0.9692	pathogenic	0.456	Stabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
E/K	0.8798	likely_pathogenic	0.9116	pathogenic	-1.024	Destabilizing	0.977	D	0.578	neutral	N	0.504986905	None	None	N
E/L	0.9755	likely_pathogenic	0.9816	pathogenic	0.456	Stabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
E/M	0.9786	likely_pathogenic	0.9837	pathogenic	0.946	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/N	0.8588	likely_pathogenic	0.8942	pathogenic	-1.517	Destabilizing	0.99	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.9955	likely_pathogenic	0.9966	pathogenic	0.083	Stabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
E/Q	0.5793	likely_pathogenic	0.6474	pathogenic	-1.286	Destabilizing	0.997	D	0.687	prob.neutral	N	0.512463255	None	None	N
E/R	0.9194	likely_pathogenic	0.9407	pathogenic	-0.761	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
E/S	0.6732	likely_pathogenic	0.76	pathogenic	-1.892	Destabilizing	0.983	D	0.601	neutral	None	None	None	None	N
E/T	0.7878	likely_pathogenic	0.8354	pathogenic	-1.533	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
E/V	0.892	likely_pathogenic	0.9116	pathogenic	0.083	Stabilizing	0.997	D	0.781	deleterious	D	0.565334174	None	None	N
E/W	0.9979	likely_pathogenic	0.9985	pathogenic	0.125	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.9879	likely_pathogenic	0.9905	pathogenic	0.181	Stabilizing	1.0	D	0.795	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.