TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1788	5587;5588;5589	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227
N2AB	1788	5587;5588;5589	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227
N2A	1788	5587;5588;5589	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227
N2B	1742	5449;5450;5451	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227
Novex-1	1742	5449;5450;5451	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227
Novex-2	1742	5449;5450;5451	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227
Novex-3	1788	5587;5588;5589	chr2:178776502;178776501;178776500	chr2:179641229;179641228;179641227

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-8
• Domain position: 86
• Structural Position: 169
• Q(SASA): 0.1101
• 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
T/I	rs760787459	0.258	1.0	D	0.879	0.531	0.602907052046	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
T/I	rs760787459	0.258	1.0	D	0.879	0.531	0.602907052046	gnomAD-4.0.0	4.12045E-06	None	None	None	None	N	None	0	0	None	0	5.03931E-05	None	0	0	3.59729E-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
T/A	0.3603	ambiguous	0.444	ambiguous	-1.049	Destabilizing	0.999	D	0.627	neutral	N	0.502445291	None	None	N
T/C	0.757	likely_pathogenic	0.848	pathogenic	-0.57	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
T/D	0.9667	likely_pathogenic	0.9714	pathogenic	-1.276	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
T/E	0.973	likely_pathogenic	0.9791	pathogenic	-1.141	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
T/F	0.9462	likely_pathogenic	0.9744	pathogenic	-0.622	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
T/G	0.7938	likely_pathogenic	0.834	pathogenic	-1.441	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
T/H	0.8951	likely_pathogenic	0.9273	pathogenic	-1.601	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
T/I	0.8636	likely_pathogenic	0.9208	pathogenic	-0.038	Destabilizing	1.0	D	0.879	deleterious	D	0.603003282	None	None	N
T/K	0.9756	likely_pathogenic	0.9815	pathogenic	-0.813	Destabilizing	1.0	D	0.85	deleterious	D	0.588362732	None	None	N
T/L	0.7136	likely_pathogenic	0.8047	pathogenic	-0.038	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
T/M	0.577	likely_pathogenic	0.6976	pathogenic	0.193	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/N	0.7067	likely_pathogenic	0.7618	pathogenic	-1.227	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/P	0.9655	likely_pathogenic	0.9661	pathogenic	-0.343	Destabilizing	1.0	D	0.875	deleterious	D	0.666718035	None	None	N
T/Q	0.9244	likely_pathogenic	0.9456	pathogenic	-1.119	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
T/R	0.9611	likely_pathogenic	0.971	pathogenic	-0.85	Destabilizing	1.0	D	0.882	deleterious	D	0.602578694	None	None	N
T/S	0.2895	likely_benign	0.2946	benign	-1.434	Destabilizing	0.999	D	0.597	neutral	N	0.473869597	None	None	N
T/V	0.6723	likely_pathogenic	0.7704	pathogenic	-0.343	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
T/W	0.9892	likely_pathogenic	0.9941	pathogenic	-0.743	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
T/Y	0.9514	likely_pathogenic	0.9749	pathogenic	-0.45	Destabilizing	1.0	D	0.918	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.