TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6016	18271;18272;18273	chr2:178730354;178730353;178730352	chr2:179595081;179595080;179595079
N2AB	5699	17320;17321;17322	chr2:178730354;178730353;178730352	chr2:179595081;179595080;179595079
N2A	4772	14539;14540;14541	chr2:178730354;178730353;178730352	chr2:179595081;179595080;179595079
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-44
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.371
• 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	0.016	N	0.205	0.043	0.281381271821	gnomAD-4.0.0	1.61325E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89665E-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	0.2079	likely_benign	0.2115	benign	-0.398	Destabilizing	0.834	D	0.637	neutral	N	0.471875012	None	None	N
E/C	0.9012	likely_pathogenic	0.8898	pathogenic	-0.252	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.1812	likely_benign	0.196	benign	-0.478	Destabilizing	0.016	N	0.205	neutral	N	0.500581766	None	None	N
E/F	0.8312	likely_pathogenic	0.833	pathogenic	-0.016	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
E/G	0.2196	likely_benign	0.2248	benign	-0.64	Destabilizing	0.946	D	0.683	prob.neutral	N	0.507950456	None	None	N
E/H	0.5494	ambiguous	0.5281	ambiguous	0.31	Stabilizing	0.994	D	0.679	prob.neutral	None	None	None	None	N
E/I	0.4389	ambiguous	0.4495	ambiguous	0.223	Stabilizing	0.979	D	0.755	deleterious	None	None	None	None	N
E/K	0.1827	likely_benign	0.171	benign	0.231	Stabilizing	0.834	D	0.544	neutral	N	0.471546939	None	None	N
E/L	0.4795	ambiguous	0.4743	ambiguous	0.223	Stabilizing	0.979	D	0.761	deleterious	None	None	None	None	N
E/M	0.5308	ambiguous	0.5325	ambiguous	0.201	Stabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/N	0.3467	ambiguous	0.3746	ambiguous	-0.309	Destabilizing	0.921	D	0.706	prob.neutral	None	None	None	None	N
E/P	0.9315	likely_pathogenic	0.9282	pathogenic	0.037	Stabilizing	0.979	D	0.758	deleterious	None	None	None	None	N
E/Q	0.1339	likely_benign	0.1313	benign	-0.227	Destabilizing	0.946	D	0.627	neutral	N	0.468293203	None	None	N
E/R	0.3158	likely_benign	0.2864	benign	0.581	Stabilizing	0.959	D	0.731	prob.delet.	None	None	None	None	N
E/S	0.2487	likely_benign	0.2712	benign	-0.458	Destabilizing	0.769	D	0.596	neutral	None	None	None	None	N
E/T	0.2625	likely_benign	0.2789	benign	-0.25	Destabilizing	0.959	D	0.735	prob.delet.	None	None	None	None	N
E/V	0.2443	likely_benign	0.2501	benign	0.037	Stabilizing	0.973	D	0.755	deleterious	N	0.453539968	None	None	N
E/W	0.9207	likely_pathogenic	0.9112	pathogenic	0.207	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/Y	0.7349	likely_pathogenic	0.7204	pathogenic	0.249	Stabilizing	0.998	D	0.727	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.