TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2760	8503;8504;8505	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239
N2AB	2760	8503;8504;8505	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239
N2A	2760	8503;8504;8505	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239
N2B	2714	8365;8366;8367	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239
Novex-1	2714	8365;8366;8367	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239
Novex-2	2714	8365;8366;8367	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239
Novex-3	2760	8503;8504;8505	chr2:178770514;178770513;178770512	chr2:179635241;179635240;179635239

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-17
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3323
• 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
T/I	None	None	0.096	D	0.438	0.142	0.412715890961	gnomAD-4.0.0	1.36814E-06	None	None	None	None	N	None	2.98686E-05	0	None	0	0	None	0	0	8.99295E-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
T/A	0.0866	likely_benign	0.09	benign	-1.015	Destabilizing	0.001	N	0.151	neutral	N	0.503698416	None	None	N
T/C	0.3817	ambiguous	0.4149	ambiguous	-0.585	Destabilizing	0.883	D	0.47	neutral	None	None	None	None	N
T/D	0.2507	likely_benign	0.2602	benign	-0.431	Destabilizing	0.124	N	0.448	neutral	None	None	None	None	N
T/E	0.2699	likely_benign	0.3196	benign	-0.317	Destabilizing	0.124	N	0.401	neutral	None	None	None	None	N
T/F	0.3257	likely_benign	0.3481	ambiguous	-0.728	Destabilizing	0.331	N	0.541	neutral	None	None	None	None	N
T/G	0.2044	likely_benign	0.2153	benign	-1.379	Destabilizing	0.124	N	0.51	neutral	None	None	None	None	N
T/H	0.2441	likely_benign	0.2626	benign	-1.475	Destabilizing	0.497	N	0.543	neutral	None	None	None	None	N
T/I	0.2601	likely_benign	0.284	benign	-0.094	Destabilizing	0.096	N	0.438	neutral	D	0.535698894	None	None	N
T/K	0.1733	likely_benign	0.2189	benign	-0.566	Destabilizing	0.001	N	0.283	neutral	N	0.485199111	None	None	N
T/L	0.124	likely_benign	0.1305	benign	-0.094	Destabilizing	0.001	N	0.227	neutral	None	None	None	None	N
T/M	0.0985	likely_benign	0.1042	benign	-0.013	Destabilizing	0.055	N	0.413	neutral	None	None	None	None	N
T/N	0.0721	likely_benign	0.0636	benign	-0.844	Destabilizing	0.002	N	0.195	neutral	None	None	None	None	N
T/P	0.1496	likely_benign	0.1616	benign	-0.368	Destabilizing	0.002	N	0.287	neutral	N	0.512624393	None	None	N
T/Q	0.1972	likely_benign	0.2276	benign	-0.786	Destabilizing	0.497	N	0.463	neutral	None	None	None	None	N
T/R	0.1457	likely_benign	0.1914	benign	-0.579	Destabilizing	0.096	N	0.45	neutral	N	0.488444825	None	None	N
T/S	0.101	likely_benign	0.097	benign	-1.181	Destabilizing	0.042	N	0.303	neutral	N	0.50662477	None	None	N
T/V	0.1981	likely_benign	0.2053	benign	-0.368	Destabilizing	0.055	N	0.279	neutral	None	None	None	None	N
T/W	0.6347	likely_pathogenic	0.6785	pathogenic	-0.725	Destabilizing	0.883	D	0.543	neutral	None	None	None	None	N
T/Y	0.2955	likely_benign	0.3196	benign	-0.437	Destabilizing	0.002	N	0.409	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.