TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3199	9820;9821;9822	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214
N2AB	3199	9820;9821;9822	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214
N2A	3199	9820;9821;9822	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214
N2B	3153	9682;9683;9684	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214
Novex-1	3153	9682;9683;9684	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214
Novex-2	3153	9682;9683;9684	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214
Novex-3	3199	9820;9821;9822	chr2:178766489;178766488;178766487	chr2:179631216;179631215;179631214

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-22
• Domain position: 53
• Structural Position: 130
• Q(SASA): 0.6768
• 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	rs2090451326	None	0.993	D	0.456	0.432	0.527251791467	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/G	rs2090451326	None	0.993	D	0.456	0.432	0.527251791467	gnomAD-4.0.0	6.56883E-06	None	None	None	None	N	None	2.4115E-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	0.7681	likely_pathogenic	0.7866	pathogenic	-0.542	Destabilizing	0.91	D	0.475	neutral	D	0.586473993	None	None	N
E/C	0.994	likely_pathogenic	0.994	pathogenic	-0.368	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
E/D	0.6177	likely_pathogenic	0.5447	ambiguous	-0.577	Destabilizing	0.993	D	0.431	neutral	N	0.496941844	None	None	N
E/F	0.9871	likely_pathogenic	0.9884	pathogenic	-0.127	Destabilizing	0.996	D	0.555	neutral	None	None	None	None	N
E/G	0.8079	likely_pathogenic	0.8254	pathogenic	-0.811	Destabilizing	0.993	D	0.456	neutral	D	0.589806444	None	None	N
E/H	0.9492	likely_pathogenic	0.9557	pathogenic	-0.026	Destabilizing	1.0	D	0.387	neutral	None	None	None	None	N
E/I	0.9283	likely_pathogenic	0.9299	pathogenic	0.159	Stabilizing	0.304	N	0.359	neutral	None	None	None	None	N
E/K	0.811	likely_pathogenic	0.8673	pathogenic	-0.138	Destabilizing	0.993	D	0.431	neutral	D	0.581899044	None	None	N
E/L	0.9424	likely_pathogenic	0.9406	pathogenic	0.159	Stabilizing	0.871	D	0.492	neutral	None	None	None	None	N
E/M	0.9496	likely_pathogenic	0.9545	pathogenic	0.219	Stabilizing	0.996	D	0.525	neutral	None	None	None	None	N
E/N	0.892	likely_pathogenic	0.8921	pathogenic	-0.575	Destabilizing	0.999	D	0.378	neutral	None	None	None	None	N
E/P	0.9968	likely_pathogenic	0.9963	pathogenic	-0.054	Destabilizing	0.999	D	0.439	neutral	None	None	None	None	N
E/Q	0.5481	ambiguous	0.6333	pathogenic	-0.482	Destabilizing	0.998	D	0.393	neutral	N	0.513640922	None	None	N
E/R	0.888	likely_pathogenic	0.914	pathogenic	0.195	Stabilizing	0.999	D	0.379	neutral	None	None	None	None	N
E/S	0.7877	likely_pathogenic	0.8029	pathogenic	-0.762	Destabilizing	0.995	D	0.399	neutral	None	None	None	None	N
E/T	0.8663	likely_pathogenic	0.8759	pathogenic	-0.543	Destabilizing	0.985	D	0.455	neutral	None	None	None	None	N
E/V	0.8387	likely_pathogenic	0.8505	pathogenic	-0.054	Destabilizing	0.835	D	0.451	neutral	N	0.513138986	None	None	N
E/W	0.9953	likely_pathogenic	0.9958	pathogenic	0.092	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/Y	0.98	likely_pathogenic	0.9815	pathogenic	0.11	Stabilizing	0.999	D	0.519	neutral	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.