TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16762	50509;50510;50511	chr2:178612127;178612126;178612125	chr2:179476854;179476853;179476852
N2AB	15121	45586;45587;45588	chr2:178612127;178612126;178612125	chr2:179476854;179476853;179476852
N2A	14194	42805;42806;42807	chr2:178612127;178612126;178612125	chr2:179476854;179476853;179476852
N2B	7697	23314;23315;23316	chr2:178612127;178612126;178612125	chr2:179476854;179476853;179476852
Novex-1	7822	23689;23690;23691	chr2:178612127;178612126;178612125	chr2:179476854;179476853;179476852
Novex-2	7889	23890;23891;23892	chr2:178612127;178612126;178612125	chr2:179476854;179476853;179476852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-10
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3871
• 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
D/N	None	None	0.801	N	0.393	0.282	0.299427821978	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.2568	likely_benign	0.4106	ambiguous	-0.513	Destabilizing	0.022	N	0.197	neutral	N	0.475937532	None	None	N
D/C	0.8423	likely_pathogenic	0.9046	pathogenic	-0.268	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	N
D/E	0.1896	likely_benign	0.2671	benign	-0.664	Destabilizing	0.005	N	0.061	neutral	N	0.427326764	None	None	N
D/F	0.8504	likely_pathogenic	0.9228	pathogenic	-0.226	Destabilizing	0.991	D	0.5	neutral	None	None	None	None	N
D/G	0.2467	likely_benign	0.3766	ambiguous	-0.819	Destabilizing	0.801	D	0.333	neutral	N	0.482006806	None	None	N
D/H	0.5376	ambiguous	0.6722	pathogenic	-0.479	Destabilizing	0.966	D	0.403	neutral	N	0.51470875	None	None	N
D/I	0.7639	likely_pathogenic	0.8859	pathogenic	0.281	Stabilizing	0.974	D	0.491	neutral	None	None	None	None	N
D/K	0.6526	likely_pathogenic	0.7876	pathogenic	-0.48	Destabilizing	0.728	D	0.332	neutral	None	None	None	None	N
D/L	0.6807	likely_pathogenic	0.8183	pathogenic	0.281	Stabilizing	0.842	D	0.431	neutral	None	None	None	None	N
D/M	0.8348	likely_pathogenic	0.9162	pathogenic	0.607	Stabilizing	0.998	D	0.489	neutral	None	None	None	None	N
D/N	0.1539	likely_benign	0.22	benign	-0.805	Destabilizing	0.801	D	0.393	neutral	N	0.474056836	None	None	N
D/P	0.9778	likely_pathogenic	0.9883	pathogenic	0.041	Stabilizing	0.974	D	0.365	neutral	None	None	None	None	N
D/Q	0.5293	ambiguous	0.6833	pathogenic	-0.691	Destabilizing	0.904	D	0.339	neutral	None	None	None	None	N
D/R	0.6616	likely_pathogenic	0.7891	pathogenic	-0.267	Destabilizing	0.949	D	0.414	neutral	None	None	None	None	N
D/S	0.1738	likely_benign	0.2728	benign	-0.995	Destabilizing	0.728	D	0.307	neutral	None	None	None	None	N
D/T	0.4185	ambiguous	0.5968	pathogenic	-0.759	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	N
D/V	0.5304	ambiguous	0.7161	pathogenic	0.041	Stabilizing	0.801	D	0.427	neutral	N	0.472370986	None	None	N
D/W	0.9689	likely_pathogenic	0.9835	pathogenic	-0.085	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
D/Y	0.5763	likely_pathogenic	0.7259	pathogenic	-0.024	Destabilizing	0.989	D	0.498	neutral	N	0.51470875	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.