TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25188	75787;75788;75789	chr2:178570570;178570569;178570568	chr2:179435297;179435296;179435295
N2AB	23547	70864;70865;70866	chr2:178570570;178570569;178570568	chr2:179435297;179435296;179435295
N2A	22620	68083;68084;68085	chr2:178570570;178570569;178570568	chr2:179435297;179435296;179435295
N2B	16123	48592;48593;48594	chr2:178570570;178570569;178570568	chr2:179435297;179435296;179435295
Novex-1	16248	48967;48968;48969	chr2:178570570;178570569;178570568	chr2:179435297;179435296;179435295
Novex-2	16315	49168;49169;49170	chr2:178570570;178570569;178570568	chr2:179435297;179435296;179435295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-134
• Domain position: 78
• Structural Position: 161
• Q(SASA): 0.1032
• 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
N/D	None	None	0.999	D	0.615	0.655	0.480198768302	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.9956	likely_pathogenic	0.9955	pathogenic	-0.682	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/C	0.9679	likely_pathogenic	0.9676	pathogenic	0.047	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
N/D	0.9888	likely_pathogenic	0.9897	pathogenic	-1.016	Destabilizing	0.999	D	0.615	neutral	D	0.550119362	None	None	N
N/E	0.998	likely_pathogenic	0.9984	pathogenic	-0.968	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
N/F	0.9989	likely_pathogenic	0.999	pathogenic	-0.704	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
N/G	0.9889	likely_pathogenic	0.9876	pathogenic	-0.966	Destabilizing	0.999	D	0.554	neutral	None	None	None	None	N
N/H	0.9816	likely_pathogenic	0.9822	pathogenic	-0.944	Destabilizing	1.0	D	0.763	deleterious	D	0.540030504	None	None	N
N/I	0.988	likely_pathogenic	0.9891	pathogenic	0.015	Stabilizing	1.0	D	0.747	deleterious	D	0.540283993	None	None	N
N/K	0.9988	likely_pathogenic	0.9989	pathogenic	-0.29	Destabilizing	1.0	D	0.743	deleterious	D	0.55087983	None	None	N
N/L	0.9831	likely_pathogenic	0.9836	pathogenic	0.015	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
N/M	0.9889	likely_pathogenic	0.9896	pathogenic	0.624	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
N/P	0.9985	likely_pathogenic	0.9988	pathogenic	-0.189	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
N/Q	0.9986	likely_pathogenic	0.9987	pathogenic	-1.025	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
N/R	0.9981	likely_pathogenic	0.9984	pathogenic	-0.225	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
N/S	0.9026	likely_pathogenic	0.8859	pathogenic	-0.772	Destabilizing	0.999	D	0.584	neutral	N	0.503515598	None	None	N
N/T	0.9539	likely_pathogenic	0.9503	pathogenic	-0.564	Destabilizing	0.999	D	0.709	prob.delet.	D	0.550372851	None	None	N
N/V	0.9858	likely_pathogenic	0.9872	pathogenic	-0.189	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
N/W	0.9996	likely_pathogenic	0.9997	pathogenic	-0.542	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
N/Y	0.9885	likely_pathogenic	0.9893	pathogenic	-0.294	Destabilizing	1.0	D	0.749	deleterious	D	0.551386809	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.