TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24898	74917;74918;74919	chr2:178571440;178571439;178571438	chr2:179436167;179436166;179436165
N2AB	23257	69994;69995;69996	chr2:178571440;178571439;178571438	chr2:179436167;179436166;179436165
N2A	22330	67213;67214;67215	chr2:178571440;178571439;178571438	chr2:179436167;179436166;179436165
N2B	15833	47722;47723;47724	chr2:178571440;178571439;178571438	chr2:179436167;179436166;179436165
Novex-1	15958	48097;48098;48099	chr2:178571440;178571439;178571438	chr2:179436167;179436166;179436165
Novex-2	16025	48298;48299;48300	chr2:178571440;178571439;178571438	chr2:179436167;179436166;179436165
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: Fn3-68
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.1138
• 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	0.003	N	0.211	0.063	0.166414681773	gnomAD-4.0.0	6.84332E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99583E-07	0	0
E/K	rs751312481	None	0.007	N	0.428	0.152	0.236278675362	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20732E-04	0	0	0	0	None	0	0	0	0	0
E/K	rs751312481	None	0.007	N	0.428	0.152	0.236278675362	gnomAD-4.0.0	7.69022E-06	None	None	None	None	N	None	1.01561E-04	0	None	0	0	None	0	0	0	0	0
E/Q	rs751312481	-0.634	0.883	N	0.699	0.178	0.19670166235	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/Q	rs751312481	-0.634	0.883	N	0.699	0.178	0.19670166235	gnomAD-4.0.0	3.18381E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7188E-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	0.0973	likely_benign	0.0946	benign	-0.264	Destabilizing	0.682	D	0.757	deleterious	N	0.464768511	None	None	N
E/C	0.6541	likely_pathogenic	0.6408	pathogenic	-0.093	Destabilizing	0.996	D	0.845	deleterious	None	None	None	None	N
E/D	0.0908	likely_benign	0.0851	benign	-0.239	Destabilizing	0.003	N	0.211	neutral	N	0.481787283	None	None	N
E/F	0.5541	ambiguous	0.5415	ambiguous	-0.204	Destabilizing	0.909	D	0.861	deleterious	None	None	None	None	N
E/G	0.1256	likely_benign	0.1265	benign	-0.432	Destabilizing	0.682	D	0.766	deleterious	N	0.500951834	None	None	N
E/H	0.3344	likely_benign	0.3203	benign	0.177	Stabilizing	0.996	D	0.702	prob.delet.	None	None	None	None	N
E/I	0.171	likely_benign	0.1671	benign	0.136	Stabilizing	0.02	N	0.725	deleterious	None	None	None	None	N
E/K	0.0888	likely_benign	0.0913	benign	0.309	Stabilizing	0.007	N	0.428	neutral	N	0.503490707	None	None	N
E/L	0.2081	likely_benign	0.1991	benign	0.136	Stabilizing	0.329	N	0.786	deleterious	None	None	None	None	N
E/M	0.2577	likely_benign	0.2551	benign	0.108	Stabilizing	0.974	D	0.77	deleterious	None	None	None	None	N
E/N	0.1648	likely_benign	0.1578	benign	0.091	Stabilizing	0.587	D	0.708	prob.delet.	None	None	None	None	N
E/P	0.208	likely_benign	0.2054	benign	0.022	Stabilizing	0.953	D	0.8	deleterious	None	None	None	None	N
E/Q	0.101	likely_benign	0.0998	benign	0.11	Stabilizing	0.883	D	0.699	prob.delet.	N	0.474607561	None	None	N
E/R	0.1712	likely_benign	0.172	benign	0.552	Stabilizing	0.833	D	0.761	deleterious	None	None	None	None	N
E/S	0.1272	likely_benign	0.121	benign	-0.094	Destabilizing	0.74	D	0.678	prob.neutral	None	None	None	None	N
E/T	0.1369	likely_benign	0.1324	benign	0.042	Stabilizing	0.74	D	0.793	deleterious	None	None	None	None	N
E/V	0.1138	likely_benign	0.1111	benign	0.022	Stabilizing	0.27	N	0.756	deleterious	N	0.477899243	None	None	N
E/W	0.8001	likely_pathogenic	0.7942	pathogenic	-0.09	Destabilizing	0.996	D	0.818	deleterious	None	None	None	None	N
E/Y	0.4271	ambiguous	0.414	ambiguous	0.031	Stabilizing	0.953	D	0.785	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.