TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19076	57451;57452;57453	chr2:178597944;178597943;178597942	chr2:179462671;179462670;179462669
N2AB	17435	52528;52529;52530	chr2:178597944;178597943;178597942	chr2:179462671;179462670;179462669
N2A	16508	49747;49748;49749	chr2:178597944;178597943;178597942	chr2:179462671;179462670;179462669
N2B	10011	30256;30257;30258	chr2:178597944;178597943;178597942	chr2:179462671;179462670;179462669
Novex-1	10136	30631;30632;30633	chr2:178597944;178597943;178597942	chr2:179462671;179462670;179462669
Novex-2	10203	30832;30833;30834	chr2:178597944;178597943;178597942	chr2:179462671;179462670;179462669
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: Fn3-26
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.3877
• 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	rs1288756593	-1.066	0.006	N	0.423	0.121	0.243972157842	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs1288756593	-1.066	0.006	N	0.423	0.121	0.243972157842	gnomAD-4.0.0	4.10642E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.95878E-05	0
E/K	None	None	0.651	N	0.425	0.268	0.265929055128	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2188	likely_benign	0.216	benign	-0.768	Destabilizing	0.651	D	0.497	neutral	N	0.507741733	None	None	N
E/C	0.8198	likely_pathogenic	0.8288	pathogenic	-0.541	Destabilizing	0.995	D	0.72	deleterious	None	None	None	None	N
E/D	0.125	likely_benign	0.1319	benign	-1.046	Destabilizing	0.006	N	0.423	neutral	N	0.493908431	None	None	N
E/F	0.6163	likely_pathogenic	0.6178	pathogenic	0.026	Stabilizing	0.018	N	0.475	neutral	None	None	None	None	N
E/G	0.3141	likely_benign	0.304	benign	-1.148	Destabilizing	0.651	D	0.592	neutral	N	0.471658273	None	None	N
E/H	0.5327	ambiguous	0.5046	ambiguous	-0.138	Destabilizing	0.946	D	0.505	neutral	None	None	None	None	N
E/I	0.2676	likely_benign	0.2813	benign	0.275	Stabilizing	0.813	D	0.687	prob.delet.	None	None	None	None	N
E/K	0.2796	likely_benign	0.2476	benign	-0.669	Destabilizing	0.651	D	0.425	neutral	N	0.513995702	None	None	N
E/L	0.324	likely_benign	0.3392	benign	0.275	Stabilizing	0.008	N	0.486	neutral	None	None	None	None	N
E/M	0.3598	ambiguous	0.3797	ambiguous	0.586	Stabilizing	0.897	D	0.655	prob.neutral	None	None	None	None	N
E/N	0.2645	likely_benign	0.2865	benign	-1.197	Destabilizing	0.813	D	0.499	neutral	None	None	None	None	N
E/P	0.7418	likely_pathogenic	0.7349	pathogenic	-0.051	Destabilizing	0.946	D	0.575	neutral	None	None	None	None	N
E/Q	0.2149	likely_benign	0.2001	benign	-1.035	Destabilizing	0.93	D	0.535	neutral	N	0.510302036	None	None	N
E/R	0.4534	ambiguous	0.4031	ambiguous	-0.263	Destabilizing	0.946	D	0.519	neutral	None	None	None	None	N
E/S	0.2527	likely_benign	0.2667	benign	-1.511	Destabilizing	0.712	D	0.4	neutral	None	None	None	None	N
E/T	0.2239	likely_benign	0.2495	benign	-1.193	Destabilizing	0.834	D	0.551	neutral	None	None	None	None	N
E/V	0.1697	likely_benign	0.1814	benign	-0.051	Destabilizing	0.483	N	0.577	neutral	N	0.465061681	None	None	N
E/W	0.8795	likely_pathogenic	0.8685	pathogenic	0.322	Stabilizing	0.995	D	0.689	prob.delet.	None	None	None	None	N
E/Y	0.5349	ambiguous	0.54	ambiguous	0.283	Stabilizing	0.071	N	0.404	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.