TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26278	79057;79058;79059	chr2:178567300;178567299;178567298	chr2:179432027;179432026;179432025
N2AB	24637	74134;74135;74136	chr2:178567300;178567299;178567298	chr2:179432027;179432026;179432025
N2A	23710	71353;71354;71355	chr2:178567300;178567299;178567298	chr2:179432027;179432026;179432025
N2B	17213	51862;51863;51864	chr2:178567300;178567299;178567298	chr2:179432027;179432026;179432025
Novex-1	17338	52237;52238;52239	chr2:178567300;178567299;178567298	chr2:179432027;179432026;179432025
Novex-2	17405	52438;52439;52440	chr2:178567300;178567299;178567298	chr2:179432027;179432026;179432025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-137
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.3736
• 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
P/A	rs1235411503	-0.853	0.885	N	0.613	0.257	0.335164054921	gnomAD-4.0.0	1.60839E-06	None	None	None	None	N	None	0	2.35106E-05	None	0	0	None	0	0	0	0	0
P/L	None	None	0.964	N	0.783	0.489	0.657223871714	gnomAD-4.0.0	2.7495E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60551E-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
P/A	0.0765	likely_benign	0.0708	benign	-1.137	Destabilizing	0.885	D	0.613	neutral	N	0.455057333	None	None	N
P/C	0.4509	ambiguous	0.3789	ambiguous	-0.808	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
P/D	0.5448	ambiguous	0.4832	ambiguous	-0.808	Destabilizing	0.986	D	0.721	prob.delet.	None	None	None	None	N
P/E	0.3471	ambiguous	0.3142	benign	-0.836	Destabilizing	0.986	D	0.721	prob.delet.	None	None	None	None	N
P/F	0.4451	ambiguous	0.3643	ambiguous	-0.896	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
P/G	0.352	ambiguous	0.2947	benign	-1.413	Destabilizing	0.953	D	0.735	prob.delet.	None	None	None	None	N
P/H	0.208	likely_benign	0.1764	benign	-0.895	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
P/I	0.2338	likely_benign	0.1987	benign	-0.504	Destabilizing	0.986	D	0.817	deleterious	None	None	None	None	N
P/K	0.3659	ambiguous	0.3292	benign	-0.985	Destabilizing	0.986	D	0.718	prob.delet.	None	None	None	None	N
P/L	0.1112	likely_benign	0.0975	benign	-0.504	Destabilizing	0.964	D	0.783	deleterious	N	0.487516469	None	None	N
P/M	0.2619	likely_benign	0.2245	benign	-0.446	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
P/N	0.334	likely_benign	0.2754	benign	-0.741	Destabilizing	0.986	D	0.805	deleterious	None	None	None	None	N
P/Q	0.1925	likely_benign	0.1719	benign	-0.918	Destabilizing	0.991	D	0.766	deleterious	N	0.452075743	None	None	N
P/R	0.2463	likely_benign	0.2185	benign	-0.456	Destabilizing	0.991	D	0.818	deleterious	N	0.4813585	None	None	N
P/S	0.1238	likely_benign	0.1066	benign	-1.231	Destabilizing	0.58	D	0.427	neutral	N	0.402761644	None	None	N
P/T	0.093	likely_benign	0.0836	benign	-1.147	Destabilizing	0.322	N	0.437	neutral	N	0.395739671	None	None	N
P/V	0.167	likely_benign	0.1449	benign	-0.679	Destabilizing	0.973	D	0.759	deleterious	None	None	None	None	N
P/W	0.6764	likely_pathogenic	0.5933	pathogenic	-1.043	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
P/Y	0.44	ambiguous	0.3692	ambiguous	-0.756	Destabilizing	0.999	D	0.817	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.