TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31008	93247;93248;93249	chr2:178548604;178548603;178548602	chr2:179413331;179413330;179413329
N2AB	29367	88324;88325;88326	chr2:178548604;178548603;178548602	chr2:179413331;179413330;179413329
N2A	28440	85543;85544;85545	chr2:178548604;178548603;178548602	chr2:179413331;179413330;179413329
N2B	21943	66052;66053;66054	chr2:178548604;178548603;178548602	chr2:179413331;179413330;179413329
Novex-1	22068	66427;66428;66429	chr2:178548604;178548603;178548602	chr2:179413331;179413330;179413329
Novex-2	22135	66628;66629;66630	chr2:178548604;178548603;178548602	chr2:179413331;179413330;179413329
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-150
• Domain position: 82
• Structural Position: 171
• Q(SASA): 0.322
• 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/R	rs1287048789	None	0.964	N	0.684	0.542	0.562354153293	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/R	rs1287048789	None	0.964	N	0.684	0.542	0.562354153293	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	6.55394E-05	None	0	0	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	0.1169	likely_benign	0.1418	benign	-1.012	Destabilizing	0.046	N	0.34	neutral	N	0.503814073	None	None	N
T/C	0.5236	ambiguous	0.5706	pathogenic	-0.549	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
T/D	0.7668	likely_pathogenic	0.8086	pathogenic	0.203	Stabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
T/E	0.7697	likely_pathogenic	0.8127	pathogenic	0.224	Stabilizing	0.953	D	0.647	neutral	None	None	None	None	N
T/F	0.4025	ambiguous	0.4494	ambiguous	-1.14	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
T/G	0.3747	ambiguous	0.4325	ambiguous	-1.273	Destabilizing	0.91	D	0.701	prob.neutral	None	None	None	None	N
T/H	0.4734	ambiguous	0.5049	ambiguous	-1.446	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
T/I	0.265	likely_benign	0.3017	benign	-0.4	Destabilizing	0.982	D	0.717	prob.delet.	D	0.530173955	None	None	N
T/K	0.6782	likely_pathogenic	0.7323	pathogenic	-0.492	Destabilizing	0.322	N	0.412	neutral	N	0.489603123	None	None	N
T/L	0.194	likely_benign	0.2288	benign	-0.4	Destabilizing	0.953	D	0.592	neutral	None	None	None	None	N
T/M	0.1336	likely_benign	0.1552	benign	-0.15	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
T/N	0.203	likely_benign	0.2456	benign	-0.491	Destabilizing	0.993	D	0.591	neutral	None	None	None	None	N
T/P	0.2721	likely_benign	0.3406	ambiguous	-0.572	Destabilizing	0.991	D	0.717	prob.delet.	N	0.489646483	None	None	N
T/Q	0.5173	ambiguous	0.5653	pathogenic	-0.592	Destabilizing	0.986	D	0.721	prob.delet.	None	None	None	None	N
T/R	0.5956	likely_pathogenic	0.6434	pathogenic	-0.334	Destabilizing	0.964	D	0.684	prob.neutral	N	0.517186015	None	None	N
T/S	0.1356	likely_benign	0.157	benign	-0.883	Destabilizing	0.885	D	0.529	neutral	N	0.457982995	None	None	N
T/V	0.1962	likely_benign	0.2232	benign	-0.572	Destabilizing	0.91	D	0.522	neutral	None	None	None	None	N
T/W	0.8201	likely_pathogenic	0.8348	pathogenic	-1.028	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
T/Y	0.4706	ambiguous	0.5137	ambiguous	-0.787	Destabilizing	0.998	D	0.796	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.