TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34972	105139;105140;105141	chr2:178531701;178531700;178531699	chr2:179396428;179396427;179396426
N2AB	33331	100216;100217;100218	chr2:178531701;178531700;178531699	chr2:179396428;179396427;179396426
N2A	32404	97435;97436;97437	chr2:178531701;178531700;178531699	chr2:179396428;179396427;179396426
N2B	25907	77944;77945;77946	chr2:178531701;178531700;178531699	chr2:179396428;179396427;179396426
Novex-1	26032	78319;78320;78321	chr2:178531701;178531700;178531699	chr2:179396428;179396427;179396426
Novex-2	26099	78520;78521;78522	chr2:178531701;178531700;178531699	chr2:179396428;179396427;179396426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-163
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.3874
• 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/A	None	None	0.505	N	0.591	0.367	0.437958778045	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	2.77239E-05	None	0	0	0	0	0
E/K	rs727504918	0.69	0.742	N	0.544	0.324	None	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	5.32E-05	0
E/K	rs727504918	0.69	0.742	N	0.544	0.324	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs727504918	0.69	0.742	N	0.544	0.324	None	gnomAD-4.0.0	3.96564E-05	None	None	None	None	N	None	1.33472E-05	0	None	0	0	None	0	0	5.25478E-05	0	1.60087E-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
E/A	0.2403	likely_benign	0.4006	ambiguous	-0.313	Destabilizing	0.505	D	0.591	neutral	N	0.51724473	None	None	N
E/C	0.9419	likely_pathogenic	0.978	pathogenic	-0.055	Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	N
E/D	0.1289	likely_benign	0.2425	benign	-0.401	Destabilizing	0.001	N	0.13	neutral	N	0.497869535	None	None	N
E/F	0.882	likely_pathogenic	0.9566	pathogenic	-0.22	Destabilizing	0.906	D	0.704	prob.neutral	None	None	None	None	N
E/G	0.381	ambiguous	0.6078	pathogenic	-0.512	Destabilizing	0.505	D	0.619	neutral	N	0.511144553	None	None	N
E/H	0.6151	likely_pathogenic	0.8191	pathogenic	0.015	Stabilizing	0.022	N	0.376	neutral	None	None	None	None	N
E/I	0.499	ambiguous	0.7238	pathogenic	0.173	Stabilizing	0.906	D	0.702	prob.neutral	None	None	None	None	N
E/K	0.2432	likely_benign	0.4578	ambiguous	0.292	Stabilizing	0.742	D	0.544	neutral	N	0.456137556	None	None	N
E/L	0.5742	likely_pathogenic	0.7732	pathogenic	0.173	Stabilizing	0.826	D	0.628	neutral	None	None	None	None	N
E/M	0.5964	likely_pathogenic	0.7781	pathogenic	0.216	Stabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
E/N	0.3001	likely_benign	0.5729	pathogenic	-0.001	Destabilizing	0.404	N	0.545	neutral	None	None	None	None	N
E/P	0.8885	likely_pathogenic	0.952	pathogenic	0.031	Stabilizing	0.906	D	0.638	neutral	None	None	None	None	N
E/Q	0.2107	likely_benign	0.3532	ambiguous	0.028	Stabilizing	0.189	N	0.244	neutral	N	0.474896675	None	None	N
E/R	0.4315	ambiguous	0.6336	pathogenic	0.507	Stabilizing	0.826	D	0.555	neutral	None	None	None	None	N
E/S	0.2704	likely_benign	0.4899	ambiguous	-0.162	Destabilizing	0.404	N	0.52	neutral	None	None	None	None	N
E/T	0.2748	likely_benign	0.5043	ambiguous	-0.004	Destabilizing	0.826	D	0.601	neutral	None	None	None	None	N
E/V	0.2926	likely_benign	0.4864	ambiguous	0.031	Stabilizing	0.879	D	0.629	neutral	N	0.50493158	None	None	N
E/W	0.9677	likely_pathogenic	0.9888	pathogenic	-0.091	Destabilizing	0.991	D	0.743	deleterious	None	None	None	None	N
E/Y	0.8116	likely_pathogenic	0.9354	pathogenic	0.019	Stabilizing	0.826	D	0.695	prob.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.