TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32378	97357;97358;97359	chr2:178542722;178542721;178542720	chr2:179407449;179407448;179407447
N2AB	30737	92434;92435;92436	chr2:178542722;178542721;178542720	chr2:179407449;179407448;179407447
N2A	29810	89653;89654;89655	chr2:178542722;178542721;178542720	chr2:179407449;179407448;179407447
N2B	23313	70162;70163;70164	chr2:178542722;178542721;178542720	chr2:179407449;179407448;179407447
Novex-1	23438	70537;70538;70539	chr2:178542722;178542721;178542720	chr2:179407449;179407448;179407447
Novex-2	23505	70738;70739;70740	chr2:178542722;178542721;178542720	chr2:179407449;179407448;179407447
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-154
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.19
• 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	None	None	None	N	0.412	0.094	0.202086224978	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85832E-06	0	0
T/P	None	None	0.741	N	0.556	0.237	0.380901646489	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	None	0	0	0	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	0.0973	likely_benign	0.085	benign	-1.191	Destabilizing	0.027	N	0.542	neutral	N	0.461976446	None	None	N
T/C	0.2932	likely_benign	0.2766	benign	-0.564	Destabilizing	0.824	D	0.549	neutral	None	None	None	None	N
T/D	0.508	ambiguous	0.4588	ambiguous	-0.674	Destabilizing	0.38	N	0.545	neutral	None	None	None	None	N
T/E	0.3107	likely_benign	0.2877	benign	-0.462	Destabilizing	0.149	N	0.531	neutral	None	None	None	None	N
T/F	0.2018	likely_benign	0.1836	benign	-0.964	Destabilizing	0.38	N	0.567	neutral	None	None	None	None	N
T/G	0.2378	likely_benign	0.2064	benign	-1.603	Destabilizing	0.149	N	0.536	neutral	None	None	None	None	N
T/H	0.1901	likely_benign	0.172	benign	-1.569	Destabilizing	0.935	D	0.571	neutral	None	None	None	None	N
T/I	0.1008	likely_benign	0.104	benign	-0.104	Destabilizing	None	N	0.412	neutral	N	0.486534168	None	None	N
T/K	0.1511	likely_benign	0.146	benign	0.103	Stabilizing	0.117	N	0.531	neutral	N	0.467775049	None	None	N
T/L	0.0799	likely_benign	0.0758	benign	-0.104	Destabilizing	0.012	N	0.51	neutral	None	None	None	None	N
T/M	0.0778	likely_benign	0.078	benign	-0.167	Destabilizing	0.035	N	0.495	neutral	None	None	None	None	N
T/N	0.1566	likely_benign	0.1398	benign	-0.534	Destabilizing	0.38	N	0.536	neutral	None	None	None	None	N
T/P	0.6012	likely_pathogenic	0.5154	ambiguous	-0.437	Destabilizing	0.741	D	0.556	neutral	N	0.47822105	None	None	N
T/Q	0.1631	likely_benign	0.1594	benign	-0.32	Destabilizing	0.555	D	0.555	neutral	None	None	None	None	N
T/R	0.1238	likely_benign	0.1087	benign	-0.202	Destabilizing	0.484	N	0.557	neutral	N	0.476951892	None	None	N
T/S	0.1157	likely_benign	0.1018	benign	-0.927	Destabilizing	0.005	N	0.431	neutral	N	0.499308677	None	None	N
T/V	0.0921	likely_benign	0.0946	benign	-0.437	Destabilizing	0.001	N	0.315	neutral	None	None	None	None	N
T/W	0.4959	ambiguous	0.4714	ambiguous	-0.978	Destabilizing	0.935	D	0.625	neutral	None	None	None	None	N
T/Y	0.2316	likely_benign	0.2155	benign	-0.601	Destabilizing	0.555	D	0.59	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.