TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6114	18565;18566;18567	chr2:178729913;178729912;178729911	chr2:179594640;179594639;179594638
N2AB	5797	17614;17615;17616	chr2:178729913;178729912;178729911	chr2:179594640;179594639;179594638
N2A	4870	14833;14834;14835	chr2:178729913;178729912;178729911	chr2:179594640;179594639;179594638
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-45
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.4091
• 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
V/A	None	None	0.012	N	0.129	0.174	0.499535901811	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/D	None	None	0.966	D	0.415	0.461	0.811599919723	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
V/I	rs762371825	-0.115	0.051	N	0.189	0.137	0.403609169532	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/I	rs762371825	-0.115	0.051	N	0.189	0.137	0.403609169532	gnomAD-4.0.0	9.58383E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.16956E-05	0	1.65804E-05

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
V/A	0.1253	likely_benign	0.1455	benign	-1.071	Destabilizing	0.012	N	0.129	neutral	N	0.509262752	None	None	I
V/C	0.6968	likely_pathogenic	0.6926	pathogenic	-0.961	Destabilizing	0.993	D	0.279	neutral	None	None	None	None	I
V/D	0.1758	likely_benign	0.2019	benign	-0.51	Destabilizing	0.966	D	0.415	neutral	D	0.534777272	None	None	I
V/E	0.1599	likely_benign	0.1782	benign	-0.46	Destabilizing	0.949	D	0.386	neutral	None	None	None	None	I
V/F	0.1014	likely_benign	0.1139	benign	-0.611	Destabilizing	0.012	N	0.177	neutral	N	0.504454365	None	None	I
V/G	0.1552	likely_benign	0.1751	benign	-1.403	Destabilizing	0.669	D	0.432	neutral	N	0.505578827	None	None	I
V/H	0.3628	ambiguous	0.4013	ambiguous	-0.8	Destabilizing	0.998	D	0.369	neutral	None	None	None	None	I
V/I	0.0757	likely_benign	0.0768	benign	-0.253	Destabilizing	0.051	N	0.189	neutral	N	0.478131768	None	None	I
V/K	0.2311	likely_benign	0.2532	benign	-0.925	Destabilizing	0.949	D	0.395	neutral	None	None	None	None	I
V/L	0.1299	likely_benign	0.1358	benign	-0.253	Destabilizing	0.005	N	0.097	neutral	N	0.489367482	None	None	I
V/M	0.11	likely_benign	0.1193	benign	-0.477	Destabilizing	0.325	N	0.215	neutral	None	None	None	None	I
V/N	0.1581	likely_benign	0.1818	benign	-0.892	Destabilizing	0.974	D	0.391	neutral	None	None	None	None	I
V/P	0.4495	ambiguous	0.4558	ambiguous	-0.491	Destabilizing	0.974	D	0.365	neutral	None	None	None	None	I
V/Q	0.2026	likely_benign	0.2268	benign	-0.898	Destabilizing	0.974	D	0.354	neutral	None	None	None	None	I
V/R	0.2064	likely_benign	0.2252	benign	-0.609	Destabilizing	0.974	D	0.401	neutral	None	None	None	None	I
V/S	0.1255	likely_benign	0.1424	benign	-1.464	Destabilizing	0.728	D	0.355	neutral	None	None	None	None	I
V/T	0.13	likely_benign	0.1467	benign	-1.279	Destabilizing	0.842	D	0.201	neutral	None	None	None	None	I
V/W	0.6445	likely_pathogenic	0.6738	pathogenic	-0.806	Destabilizing	0.998	D	0.383	neutral	None	None	None	None	I
V/Y	0.3491	ambiguous	0.3646	ambiguous	-0.484	Destabilizing	0.904	D	0.34	neutral	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.