TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7062	21409;21410;21411	chr2:178724075;178724074;178724073	chr2:179588802;179588801;179588800
N2AB	6745	20458;20459;20460	chr2:178724075;178724074;178724073	chr2:179588802;179588801;179588800
N2A	5818	17677;17678;17679	chr2:178724075;178724074;178724073	chr2:179588802;179588801;179588800
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-55
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3926
• 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
I/L	None	None	0.001	N	0.255	0.068	0.0884992946249	gnomAD-4.0.0	6.84382E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99611E-07	0	0
I/T	None	None	0.351	N	0.455	0.198	0.376393476264	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79923E-06	0	0
I/V	rs766548354	-0.62	0.001	N	0.24	0.042	0.128392430309	gnomAD-4.0.0	1.36876E-06	None	None	None	None	N	None	0	0	None	0	2.52232E-05	None	0	0	8.99611E-07	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
I/A	0.1818	likely_benign	0.1692	benign	-1.103	Destabilizing	0.129	N	0.428	neutral	None	None	None	None	N
I/C	0.4716	ambiguous	0.4635	ambiguous	-0.645	Destabilizing	0.951	D	0.496	neutral	None	None	None	None	N
I/D	0.3638	ambiguous	0.3452	ambiguous	-0.575	Destabilizing	0.264	N	0.504	neutral	None	None	None	None	N
I/E	0.3143	likely_benign	0.3113	benign	-0.641	Destabilizing	0.01	N	0.443	neutral	None	None	None	None	N
I/F	0.0941	likely_benign	0.0889	benign	-0.901	Destabilizing	0.655	D	0.471	neutral	N	0.450090578	None	None	N
I/G	0.3732	ambiguous	0.3589	ambiguous	-1.339	Destabilizing	0.593	D	0.499	neutral	None	None	None	None	N
I/H	0.2181	likely_benign	0.216	benign	-0.583	Destabilizing	0.002	N	0.458	neutral	None	None	None	None	N
I/K	0.1728	likely_benign	0.1874	benign	-0.693	Destabilizing	0.418	N	0.503	neutral	None	None	None	None	N
I/L	0.0768	likely_benign	0.0772	benign	-0.571	Destabilizing	0.001	N	0.255	neutral	N	0.392850429	None	None	N
I/M	0.0896	likely_benign	0.0855	benign	-0.427	Destabilizing	0.655	D	0.495	neutral	N	0.452861524	None	None	N
I/N	0.1247	likely_benign	0.1276	benign	-0.406	Destabilizing	0.351	N	0.551	neutral	N	0.439142866	None	None	N
I/P	0.5871	likely_pathogenic	0.5217	ambiguous	-0.715	Destabilizing	0.94	D	0.557	neutral	None	None	None	None	N
I/Q	0.2051	likely_benign	0.2121	benign	-0.651	Destabilizing	0.716	D	0.556	neutral	None	None	None	None	N
I/R	0.1228	likely_benign	0.1314	benign	-0.069	Destabilizing	0.716	D	0.565	neutral	None	None	None	None	N
I/S	0.1252	likely_benign	0.1254	benign	-0.92	Destabilizing	0.351	N	0.514	neutral	N	0.380441279	None	None	N
I/T	0.1172	likely_benign	0.1162	benign	-0.876	Destabilizing	0.351	N	0.455	neutral	N	0.346517919	None	None	N
I/V	0.0667	likely_benign	0.0657	benign	-0.715	Destabilizing	0.001	N	0.24	neutral	N	0.345384556	None	None	N
I/W	0.5559	ambiguous	0.5168	ambiguous	-0.915	Destabilizing	0.983	D	0.537	neutral	None	None	None	None	N
I/Y	0.2837	likely_benign	0.2801	benign	-0.692	Destabilizing	0.418	N	0.546	neutral	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.