TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33683	101272;101273;101274	chr2:178535568;178535567;178535566	chr2:179400295;179400294;179400293
N2AB	32042	96349;96350;96351	chr2:178535568;178535567;178535566	chr2:179400295;179400294;179400293
N2A	31115	93568;93569;93570	chr2:178535568;178535567;178535566	chr2:179400295;179400294;179400293
N2B	24618	74077;74078;74079	chr2:178535568;178535567;178535566	chr2:179400295;179400294;179400293
Novex-1	24743	74452;74453;74454	chr2:178535568;178535567;178535566	chr2:179400295;179400294;179400293
Novex-2	24810	74653;74654;74655	chr2:178535568;178535567;178535566	chr2:179400295;179400294;179400293
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-159
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.1762
• 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/K	rs747577276	-1.047	0.999	N	0.655	0.475	0.499218193508	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.30719E-04	None	0	0	0
E/K	rs747577276	-1.047	0.999	N	0.655	0.475	0.499218193508	gnomAD-4.0.0	4.78944E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11538E-05	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	0.5386	ambiguous	0.3811	ambiguous	-0.936	Destabilizing	0.998	D	0.741	deleterious	N	0.51327092	None	None	N
E/C	0.9723	likely_pathogenic	0.9431	pathogenic	-0.499	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/D	0.7176	likely_pathogenic	0.5832	pathogenic	-1.229	Destabilizing	0.988	D	0.508	neutral	N	0.517476803	None	None	N
E/F	0.968	likely_pathogenic	0.9286	pathogenic	-0.318	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/G	0.7764	likely_pathogenic	0.6183	pathogenic	-1.349	Destabilizing	1.0	D	0.789	deleterious	N	0.502928573	None	None	N
E/H	0.9176	likely_pathogenic	0.8344	pathogenic	-0.709	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/I	0.8575	likely_pathogenic	0.7216	pathogenic	0.207	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/K	0.7617	likely_pathogenic	0.5756	pathogenic	-0.85	Destabilizing	0.999	D	0.655	neutral	N	0.513761707	None	None	N
E/L	0.861	likely_pathogenic	0.7414	pathogenic	0.207	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/M	0.8532	likely_pathogenic	0.7343	pathogenic	0.779	Stabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
E/N	0.8439	likely_pathogenic	0.704	pathogenic	-1.304	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/P	0.9443	likely_pathogenic	0.8874	pathogenic	-0.153	Destabilizing	0.997	D	0.831	deleterious	None	None	None	None	N
E/Q	0.4797	ambiguous	0.3458	ambiguous	-1.118	Destabilizing	1.0	D	0.67	neutral	N	0.504488863	None	None	N
E/R	0.8223	likely_pathogenic	0.6873	pathogenic	-0.615	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/S	0.7045	likely_pathogenic	0.5286	ambiguous	-1.718	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
E/T	0.7561	likely_pathogenic	0.5652	pathogenic	-1.368	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/V	0.6917	likely_pathogenic	0.5242	ambiguous	-0.153	Destabilizing	0.999	D	0.83	deleterious	D	0.528693874	None	None	N
E/W	0.9923	likely_pathogenic	0.9834	pathogenic	-0.097	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9511	likely_pathogenic	0.8965	pathogenic	-0.071	Destabilizing	1.0	D	0.828	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.