TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8384	25375;25376;25377	chr2:178717724;178717723;178717722	chr2:179582451;179582450;179582449
N2AB	8067	24424;24425;24426	chr2:178717724;178717723;178717722	chr2:179582451;179582450;179582449
N2A	7140	21643;21644;21645	chr2:178717724;178717723;178717722	chr2:179582451;179582450;179582449
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-69
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5112
• 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
N/H	None	None	0.969	N	0.302	0.209	0.282179105231	gnomAD-4.0.0	4.77702E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57947E-06	0	0
N/S	rs1191447167	None	0.015	N	0.123	0.101	0.165133752707	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
N/S	rs1191447167	None	0.015	N	0.123	0.101	0.165133752707	gnomAD-4.0.0	3.18466E-06	None	None	None	None	I	None	0	0	None	0	2.77469E-05	None	0	0	0	1.43361E-05	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	0.2048	likely_benign	0.2942	benign	-0.839	Destabilizing	0.002	N	0.241	neutral	None	None	None	None	I
N/C	0.4042	ambiguous	0.5416	ambiguous	0.025	Stabilizing	0.989	D	0.296	neutral	None	None	None	None	I
N/D	0.1716	likely_benign	0.2416	benign	0.086	Stabilizing	0.278	N	0.187	neutral	N	0.464351607	None	None	I
N/E	0.4238	ambiguous	0.5703	pathogenic	0.181	Stabilizing	0.459	N	0.174	neutral	None	None	None	None	I
N/F	0.4705	ambiguous	0.6193	pathogenic	-0.608	Destabilizing	0.982	D	0.403	neutral	None	None	None	None	I
N/G	0.284	likely_benign	0.3852	ambiguous	-1.165	Destabilizing	0.81	D	0.223	neutral	None	None	None	None	I
N/H	0.1127	likely_benign	0.1457	benign	-0.702	Destabilizing	0.969	D	0.302	neutral	N	0.503024639	None	None	I
N/I	0.2184	likely_benign	0.3169	benign	-0.015	Destabilizing	0.013	N	0.271	neutral	N	0.492095569	None	None	I
N/K	0.3819	ambiguous	0.5358	ambiguous	-0.007	Destabilizing	0.061	N	0.115	neutral	N	0.468255917	None	None	I
N/L	0.2225	likely_benign	0.3195	benign	-0.015	Destabilizing	0.543	D	0.255	neutral	None	None	None	None	I
N/M	0.3343	likely_benign	0.4505	ambiguous	0.253	Stabilizing	0.953	D	0.311	neutral	None	None	None	None	I
N/P	0.832	likely_pathogenic	0.894	pathogenic	-0.261	Destabilizing	0.715	D	0.359	neutral	None	None	None	None	I
N/Q	0.3543	ambiguous	0.4795	ambiguous	-0.534	Destabilizing	0.183	N	0.162	neutral	None	None	None	None	I
N/R	0.3462	ambiguous	0.4935	ambiguous	-0.003	Destabilizing	0.885	D	0.148	neutral	None	None	None	None	I
N/S	0.0651	likely_benign	0.0759	benign	-0.703	Destabilizing	0.015	N	0.123	neutral	N	0.431641756	None	None	I
N/T	0.1045	likely_benign	0.1315	benign	-0.405	Destabilizing	0.019	N	0.114	neutral	N	0.416096301	None	None	I
N/V	0.2366	likely_benign	0.3356	benign	-0.261	Destabilizing	0.091	N	0.291	neutral	None	None	None	None	I
N/W	0.76	likely_pathogenic	0.8628	pathogenic	-0.339	Destabilizing	0.1	N	0.277	neutral	None	None	None	None	I
N/Y	0.1873	likely_benign	0.2596	benign	-0.136	Destabilizing	0.976	D	0.401	neutral	N	0.515319145	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.