TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19726	59401;59402;59403	chr2:178592943;178592942;178592941	chr2:179457670;179457669;179457668
N2AB	18085	54478;54479;54480	chr2:178592943;178592942;178592941	chr2:179457670;179457669;179457668
N2A	17158	51697;51698;51699	chr2:178592943;178592942;178592941	chr2:179457670;179457669;179457668
N2B	10661	32206;32207;32208	chr2:178592943;178592942;178592941	chr2:179457670;179457669;179457668
Novex-1	10786	32581;32582;32583	chr2:178592943;178592942;178592941	chr2:179457670;179457669;179457668
Novex-2	10853	32782;32783;32784	chr2:178592943;178592942;178592941	chr2:179457670;179457669;179457668
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: Fn3-31
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.776
• 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	rs1356102019	None	0.834	N	0.611	0.259	0.27479166964	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs1356102019	None	0.834	N	0.611	0.259	0.27479166964	gnomAD-4.0.0	3.09903E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.2387E-06	0	0
E/Q	None	None	0.946	N	0.599	0.298	0.318252033908	gnomAD-4.0.0	6.84291E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99582E-07	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	0.1233	likely_benign	0.1223	benign	-0.302	Destabilizing	0.834	D	0.632	neutral	N	0.516134717	None	None	N
E/C	0.6943	likely_pathogenic	0.7178	pathogenic	-0.235	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
E/D	0.0918	likely_benign	0.0872	benign	-0.21	Destabilizing	0.016	N	0.388	neutral	N	0.451795237	None	None	N
E/F	0.5524	ambiguous	0.5803	pathogenic	-0.197	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
E/G	0.1372	likely_benign	0.1367	benign	-0.479	Destabilizing	0.946	D	0.599	neutral	N	0.499375753	None	None	N
E/H	0.3678	ambiguous	0.379	ambiguous	0.186	Stabilizing	0.994	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.2002	likely_benign	0.2016	benign	0.126	Stabilizing	0.979	D	0.752	deleterious	None	None	None	None	N
E/K	0.1511	likely_benign	0.1489	benign	0.12	Stabilizing	0.834	D	0.611	neutral	N	0.434710986	None	None	N
E/L	0.2688	likely_benign	0.2727	benign	0.126	Stabilizing	0.979	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.3184	likely_benign	0.3225	benign	0.031	Stabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
E/N	0.1612	likely_benign	0.1597	benign	-0.033	Destabilizing	0.921	D	0.663	neutral	None	None	None	None	N
E/P	0.4864	ambiguous	0.5367	ambiguous	0.003	Stabilizing	0.979	D	0.663	neutral	None	None	None	None	N
E/Q	0.139	likely_benign	0.1448	benign	-0.007	Destabilizing	0.946	D	0.599	neutral	N	0.498722392	None	None	N
E/R	0.2699	likely_benign	0.2744	benign	0.419	Stabilizing	0.959	D	0.673	neutral	None	None	None	None	N
E/S	0.1631	likely_benign	0.1621	benign	-0.253	Destabilizing	0.769	D	0.618	neutral	None	None	None	None	N
E/T	0.1481	likely_benign	0.1489	benign	-0.113	Destabilizing	0.959	D	0.655	neutral	None	None	None	None	N
E/V	0.1315	likely_benign	0.1275	benign	0.003	Stabilizing	0.973	D	0.695	prob.neutral	N	0.508920743	None	None	N
E/W	0.7973	likely_pathogenic	0.8197	pathogenic	-0.078	Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
E/Y	0.4533	ambiguous	0.4665	ambiguous	0.029	Stabilizing	0.998	D	0.707	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.