TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27026	81301;81302;81303	chr2:178565056;178565055;178565054	chr2:179429783;179429782;179429781
N2AB	25385	76378;76379;76380	chr2:178565056;178565055;178565054	chr2:179429783;179429782;179429781
N2A	24458	73597;73598;73599	chr2:178565056;178565055;178565054	chr2:179429783;179429782;179429781
N2B	17961	54106;54107;54108	chr2:178565056;178565055;178565054	chr2:179429783;179429782;179429781
Novex-1	18086	54481;54482;54483	chr2:178565056;178565055;178565054	chr2:179429783;179429782;179429781
Novex-2	18153	54682;54683;54684	chr2:178565056;178565055;178565054	chr2:179429783;179429782;179429781
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-84
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.7316
• Predicted PPI site: I

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
T/I	rs1371024440	None	0.942	N	0.54	0.453	0.514358602855	gnomAD-4.0.0	1.59159E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02425E-05

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
T/A	0.1344	likely_benign	0.1089	benign	-0.313	Destabilizing	0.014	N	0.16	neutral	N	0.480192559	None	None	I
T/C	0.7926	likely_pathogenic	0.7506	pathogenic	-0.173	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
T/D	0.9413	likely_pathogenic	0.9314	pathogenic	0.075	Stabilizing	0.956	D	0.526	neutral	None	None	None	None	I
T/E	0.9249	likely_pathogenic	0.9087	pathogenic	-0.018	Destabilizing	0.956	D	0.513	neutral	None	None	None	None	I
T/F	0.7962	likely_pathogenic	0.7791	pathogenic	-0.894	Destabilizing	0.978	D	0.589	neutral	None	None	None	None	I
T/G	0.5224	ambiguous	0.474	ambiguous	-0.411	Destabilizing	0.019	N	0.267	neutral	None	None	None	None	I
T/H	0.8118	likely_pathogenic	0.7751	pathogenic	-0.728	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	I
T/I	0.7973	likely_pathogenic	0.7726	pathogenic	-0.178	Destabilizing	0.942	D	0.54	neutral	N	0.475104994	None	None	I
T/K	0.864	likely_pathogenic	0.8426	pathogenic	-0.265	Destabilizing	0.942	D	0.519	neutral	N	0.513438341	None	None	I
T/L	0.3762	ambiguous	0.3276	benign	-0.178	Destabilizing	0.86	D	0.517	neutral	None	None	None	None	I
T/M	0.2189	likely_benign	0.1927	benign	0.077	Stabilizing	0.998	D	0.531	neutral	None	None	None	None	I
T/N	0.496	ambiguous	0.4351	ambiguous	-0.02	Destabilizing	0.956	D	0.501	neutral	None	None	None	None	I
T/P	0.6834	likely_pathogenic	0.6464	pathogenic	-0.196	Destabilizing	0.97	D	0.543	neutral	N	0.511184683	None	None	I
T/Q	0.7587	likely_pathogenic	0.6993	pathogenic	-0.299	Destabilizing	0.978	D	0.529	neutral	None	None	None	None	I
T/R	0.8089	likely_pathogenic	0.7899	pathogenic	0.025	Stabilizing	0.97	D	0.541	neutral	N	0.507013801	None	None	I
T/S	0.2953	likely_benign	0.2504	benign	-0.213	Destabilizing	0.698	D	0.517	neutral	N	0.447944068	None	None	I
T/V	0.5295	ambiguous	0.4855	ambiguous	-0.196	Destabilizing	0.754	D	0.484	neutral	None	None	None	None	I
T/W	0.9635	likely_pathogenic	0.9556	pathogenic	-0.902	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	I
T/Y	0.8508	likely_pathogenic	0.8269	pathogenic	-0.608	Destabilizing	0.993	D	0.594	neutral	None	None	None	None	I

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.