TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25909	77950;77951;77952	chr2:178568407;178568406;178568405	chr2:179433134;179433133;179433132
N2AB	24268	73027;73028;73029	chr2:178568407;178568406;178568405	chr2:179433134;179433133;179433132
N2A	23341	70246;70247;70248	chr2:178568407;178568406;178568405	chr2:179433134;179433133;179433132
N2B	16844	50755;50756;50757	chr2:178568407;178568406;178568405	chr2:179433134;179433133;179433132
Novex-1	16969	51130;51131;51132	chr2:178568407;178568406;178568405	chr2:179433134;179433133;179433132
Novex-2	17036	51331;51332;51333	chr2:178568407;178568406;178568405	chr2:179433134;179433133;179433132
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: Fn3-76
• Domain position: 20
• Structural Position: 21
• Q(SASA): 0.1275
• 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/A	None	None	0.919	N	0.541	0.262	0.213573922156	gnomAD-4.0.0	6.84454E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-07	0	0
T/P	None	None	0.998	N	0.761	0.459	0.457922657367	gnomAD-4.0.0	1.36891E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79926E-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	0.1295	likely_benign	0.1368	benign	-0.886	Destabilizing	0.919	D	0.541	neutral	N	0.471510597	None	None	N
T/C	0.3205	likely_benign	0.2819	benign	-1.037	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/D	0.7569	likely_pathogenic	0.7869	pathogenic	-1.652	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	N
T/E	0.6263	likely_pathogenic	0.674	pathogenic	-1.561	Destabilizing	0.995	D	0.718	prob.delet.	None	None	None	None	N
T/F	0.278	likely_benign	0.2875	benign	-0.989	Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
T/G	0.4175	ambiguous	0.4462	ambiguous	-1.187	Destabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	N
T/H	0.3517	ambiguous	0.3579	ambiguous	-1.49	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/I	0.1174	likely_benign	0.1272	benign	-0.154	Destabilizing	0.919	D	0.662	neutral	N	0.512614409	None	None	N
T/K	0.4386	ambiguous	0.4842	ambiguous	-0.721	Destabilizing	0.994	D	0.725	prob.delet.	N	0.47949954	None	None	N
T/L	0.1002	likely_benign	0.1032	benign	-0.154	Destabilizing	0.938	D	0.592	neutral	None	None	None	None	N
T/M	0.0896	likely_benign	0.0871	benign	0.018	Stabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
T/N	0.1932	likely_benign	0.2096	benign	-1.202	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
T/P	0.7732	likely_pathogenic	0.8298	pathogenic	-0.367	Destabilizing	0.998	D	0.761	deleterious	N	0.5116199	None	None	N
T/Q	0.3793	ambiguous	0.3957	ambiguous	-1.308	Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
T/R	0.3692	ambiguous	0.4023	ambiguous	-0.593	Destabilizing	0.994	D	0.773	deleterious	N	0.479561993	None	None	N
T/S	0.1406	likely_benign	0.1389	benign	-1.318	Destabilizing	0.979	D	0.545	neutral	N	0.482502146	None	None	N
T/V	0.0973	likely_benign	0.097	benign	-0.367	Destabilizing	0.086	N	0.423	neutral	None	None	None	None	N
T/W	0.7016	likely_pathogenic	0.6977	pathogenic	-1.067	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
T/Y	0.3521	ambiguous	0.3544	ambiguous	-0.69	Destabilizing	0.995	D	0.84	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.