TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25028	75307;75308;75309	chr2:178571050;178571049;178571048	chr2:179435777;179435776;179435775
N2AB	23387	70384;70385;70386	chr2:178571050;178571049;178571048	chr2:179435777;179435776;179435775
N2A	22460	67603;67604;67605	chr2:178571050;178571049;178571048	chr2:179435777;179435776;179435775
N2B	15963	48112;48113;48114	chr2:178571050;178571049;178571048	chr2:179435777;179435776;179435775
Novex-1	16088	48487;48488;48489	chr2:178571050;178571049;178571048	chr2:179435777;179435776;179435775
Novex-2	16155	48688;48689;48690	chr2:178571050;178571049;178571048	chr2:179435777;179435776;179435775
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-70
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4789
• 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
K/R	rs1708004980	None	0.491	N	0.452	0.147	0.228597637076	gnomAD-4.0.0	4.10883E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.40173E-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
K/A	0.2702	likely_benign	0.2624	benign	-0.124	Destabilizing	0.103	N	0.255	neutral	None	None	None	None	N
K/C	0.6233	likely_pathogenic	0.6117	pathogenic	-0.157	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	N
K/D	0.4091	ambiguous	0.3752	ambiguous	0.06	Stabilizing	0.561	D	0.498	neutral	None	None	None	None	N
K/E	0.1236	likely_benign	0.1184	benign	0.102	Stabilizing	0.285	N	0.465	neutral	N	0.454179394	None	None	N
K/F	0.7557	likely_pathogenic	0.7315	pathogenic	-0.077	Destabilizing	0.901	D	0.592	neutral	None	None	None	None	N
K/G	0.3317	likely_benign	0.3091	benign	-0.401	Destabilizing	0.345	N	0.439	neutral	None	None	None	None	N
K/H	0.2878	likely_benign	0.2685	benign	-0.742	Destabilizing	0.965	D	0.573	neutral	None	None	None	None	N
K/I	0.3867	ambiguous	0.365	ambiguous	0.55	Stabilizing	0.561	D	0.601	neutral	None	None	None	None	N
K/L	0.3163	likely_benign	0.2938	benign	0.55	Stabilizing	0.209	N	0.44	neutral	None	None	None	None	N
K/M	0.1904	likely_benign	0.1817	benign	0.35	Stabilizing	0.954	D	0.573	neutral	N	0.514846638	None	None	N
K/N	0.2815	likely_benign	0.2627	benign	0.13	Stabilizing	0.491	N	0.459	neutral	N	0.502146699	None	None	N
K/P	0.7016	likely_pathogenic	0.682	pathogenic	0.355	Stabilizing	0.722	D	0.607	neutral	None	None	None	None	N
K/Q	0.1003	likely_benign	0.0971	benign	-0.019	Destabilizing	0.662	D	0.529	neutral	N	0.470015638	None	None	N
K/R	0.0833	likely_benign	0.0814	benign	-0.227	Destabilizing	0.491	N	0.452	neutral	N	0.499530469	None	None	N
K/S	0.2827	likely_benign	0.2714	benign	-0.403	Destabilizing	0.021	N	0.155	neutral	None	None	None	None	N
K/T	0.1156	likely_benign	0.1117	benign	-0.19	Destabilizing	None	N	0.267	neutral	N	0.40065434	None	None	N
K/V	0.3178	likely_benign	0.3019	benign	0.355	Stabilizing	0.209	N	0.473	neutral	None	None	None	None	N
K/W	0.751	likely_pathogenic	0.7363	pathogenic	-0.027	Destabilizing	0.991	D	0.56	neutral	None	None	None	None	N
K/Y	0.6088	likely_pathogenic	0.5794	pathogenic	0.283	Stabilizing	0.965	D	0.595	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.