TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32484	97675;97676;97677	chr2:178542306;178542305;178542304	chr2:179407033;179407032;179407031
N2AB	30843	92752;92753;92754	chr2:178542306;178542305;178542304	chr2:179407033;179407032;179407031
N2A	29916	89971;89972;89973	chr2:178542306;178542305;178542304	chr2:179407033;179407032;179407031
N2B	23419	70480;70481;70482	chr2:178542306;178542305;178542304	chr2:179407033;179407032;179407031
Novex-1	23544	70855;70856;70857	chr2:178542306;178542305;178542304	chr2:179407033;179407032;179407031
Novex-2	23611	71056;71057;71058	chr2:178542306;178542305;178542304	chr2:179407033;179407032;179407031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-124
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.456
• Predicted PPI site: I

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
S/C	None	None	1.0	N	0.697	0.358	0.294561560033	gnomAD-4.0.0	1.3699E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.32807E-05	0
S/F	rs1462608160	None	0.994	N	0.705	0.317	0.442977140156	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/F	rs1462608160	None	0.994	N	0.705	0.317	0.442977140156	gnomAD-4.0.0	1.24063E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69617E-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
S/A	0.0909	likely_benign	0.0785	benign	-0.773	Destabilizing	0.835	D	0.481	neutral	N	0.396061305	None	None	I
S/C	0.1393	likely_benign	0.1187	benign	-0.492	Destabilizing	1.0	D	0.697	prob.neutral	N	0.502210122	None	None	I
S/D	0.3394	likely_benign	0.2904	benign	0.036	Stabilizing	0.985	D	0.556	neutral	None	None	None	None	I
S/E	0.4495	ambiguous	0.402	ambiguous	0.01	Stabilizing	0.97	D	0.553	neutral	None	None	None	None	I
S/F	0.2988	likely_benign	0.2262	benign	-0.967	Destabilizing	0.994	D	0.705	prob.neutral	N	0.483104287	None	None	I
S/G	0.0818	likely_benign	0.0736	benign	-0.995	Destabilizing	0.041	N	0.187	neutral	None	None	None	None	I
S/H	0.366	ambiguous	0.3047	benign	-1.373	Destabilizing	0.191	N	0.337	neutral	None	None	None	None	I
S/I	0.2223	likely_benign	0.1742	benign	-0.293	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
S/K	0.6574	likely_pathogenic	0.5744	pathogenic	-0.679	Destabilizing	0.985	D	0.568	neutral	None	None	None	None	I
S/L	0.1327	likely_benign	0.1043	benign	-0.293	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	I
S/M	0.2373	likely_benign	0.1977	benign	-0.044	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
S/N	0.1138	likely_benign	0.0965	benign	-0.52	Destabilizing	0.97	D	0.555	neutral	None	None	None	None	I
S/P	0.1108	likely_benign	0.0979	benign	-0.421	Destabilizing	0.998	D	0.697	prob.neutral	N	0.352134383	None	None	I
S/Q	0.4543	ambiguous	0.3998	ambiguous	-0.708	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	I
S/R	0.6133	likely_pathogenic	0.5173	ambiguous	-0.507	Destabilizing	0.996	D	0.696	prob.neutral	None	None	None	None	I
S/T	0.0927	likely_benign	0.0819	benign	-0.62	Destabilizing	0.98	D	0.551	neutral	N	0.417226011	None	None	I
S/V	0.2086	likely_benign	0.1697	benign	-0.421	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
S/W	0.4635	ambiguous	0.3642	ambiguous	-0.891	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
S/Y	0.2642	likely_benign	0.204	benign	-0.659	Destabilizing	0.989	D	0.708	prob.delet.	N	0.501690047	None	None	I

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.