TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21207	63844;63845;63846	chr2:178587690;178587689;178587688	chr2:179452417;179452416;179452415
N2AB	19566	58921;58922;58923	chr2:178587690;178587689;178587688	chr2:179452417;179452416;179452415
N2A	18639	56140;56141;56142	chr2:178587690;178587689;178587688	chr2:179452417;179452416;179452415
N2B	12142	36649;36650;36651	chr2:178587690;178587689;178587688	chr2:179452417;179452416;179452415
Novex-1	12267	37024;37025;37026	chr2:178587690;178587689;178587688	chr2:179452417;179452416;179452415
Novex-2	12334	37225;37226;37227	chr2:178587690;178587689;178587688	chr2:179452417;179452416;179452415
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-123
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.3952
• 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
T/P	None	None	1.0	D	0.727	0.604	0.498705051145	gnomAD-4.0.0	1.59309E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86085E-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	0.1156	likely_benign	0.1126	benign	-0.878	Destabilizing	0.996	D	0.501	neutral	N	0.501443635	None	None	I
T/C	0.4535	ambiguous	0.4732	ambiguous	-0.542	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
T/D	0.6088	likely_pathogenic	0.5599	ambiguous	-0.092	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	I
T/E	0.4223	ambiguous	0.386	ambiguous	-0.012	Destabilizing	0.994	D	0.585	neutral	None	None	None	None	I
T/F	0.2863	likely_benign	0.2723	benign	-0.748	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
T/G	0.3817	ambiguous	0.3863	ambiguous	-1.21	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
T/H	0.3254	likely_benign	0.312	benign	-1.372	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
T/I	0.1604	likely_benign	0.1576	benign	-0.061	Destabilizing	1.0	D	0.726	prob.delet.	N	0.507586154	None	None	I
T/K	0.34	ambiguous	0.315	benign	-0.545	Destabilizing	0.994	D	0.615	neutral	None	None	None	None	I
T/L	0.1146	likely_benign	0.115	benign	-0.061	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	I
T/M	0.1059	likely_benign	0.1063	benign	None	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
T/N	0.1767	likely_benign	0.1697	benign	-0.721	Destabilizing	0.999	D	0.625	neutral	D	0.523195194	None	None	I
T/P	0.627	likely_pathogenic	0.6084	pathogenic	-0.3	Destabilizing	1.0	D	0.727	prob.delet.	D	0.546668273	None	None	I
T/Q	0.2889	likely_benign	0.276	benign	-0.692	Destabilizing	0.967	D	0.429	neutral	None	None	None	None	I
T/R	0.3052	likely_benign	0.2743	benign	-0.521	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
T/S	0.1371	likely_benign	0.1327	benign	-1.058	Destabilizing	0.996	D	0.485	neutral	N	0.500616265	None	None	I
T/V	0.1432	likely_benign	0.1422	benign	-0.3	Destabilizing	0.998	D	0.528	neutral	None	None	None	None	I
T/W	0.6961	likely_pathogenic	0.6891	pathogenic	-0.731	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
T/Y	0.35	ambiguous	0.3373	benign	-0.45	Destabilizing	1.0	D	0.748	deleterious	None	None	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.