TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18262	55009;55010;55011	chr2:178603903;178603902;178603901	chr2:179468630;179468629;179468628
N2AB	16621	50086;50087;50088	chr2:178603903;178603902;178603901	chr2:179468630;179468629;179468628
N2A	15694	47305;47306;47307	chr2:178603903;178603902;178603901	chr2:179468630;179468629;179468628
N2B	9197	27814;27815;27816	chr2:178603903;178603902;178603901	chr2:179468630;179468629;179468628
Novex-1	9322	28189;28190;28191	chr2:178603903;178603902;178603901	chr2:179468630;179468629;179468628
Novex-2	9389	28390;28391;28392	chr2:178603903;178603902;178603901	chr2:179468630;179468629;179468628
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: Fn3-20
• Domain position: 97
• Structural Position: 125
• Q(SASA): 0.8556
• 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/G	None	None	0.991	N	0.78	0.326	0.326881540566	gnomAD-4.0.0	1.6019E-06	None	None	None	None	N	None	0	0	None	0	2.78676E-05	None	0	0	0	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	0.1617	likely_benign	0.1367	benign	-0.209	Destabilizing	0.982	D	0.709	prob.delet.	N	0.461486582	None	None	N
D/C	0.6111	likely_pathogenic	0.5391	ambiguous	0.048	Stabilizing	1.0	D	0.723	deleterious	None	None	None	None	N
D/E	0.1318	likely_benign	0.1105	benign	-0.283	Destabilizing	0.429	N	0.229	neutral	N	0.395242947	None	None	N
D/F	0.5783	likely_pathogenic	0.4831	ambiguous	-0.221	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	N
D/G	0.2527	likely_benign	0.2031	benign	-0.408	Destabilizing	0.991	D	0.78	deleterious	N	0.493060282	None	None	N
D/H	0.3357	likely_benign	0.2506	benign	-0.158	Destabilizing	1.0	D	0.719	prob.delet.	N	0.487517121	None	None	N
D/I	0.2547	likely_benign	0.2124	benign	0.264	Stabilizing	0.999	D	0.721	deleterious	None	None	None	None	N
D/K	0.31	likely_benign	0.2635	benign	0.191	Stabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
D/L	0.2721	likely_benign	0.2283	benign	0.264	Stabilizing	0.998	D	0.723	deleterious	None	None	None	None	N
D/M	0.5123	ambiguous	0.4281	ambiguous	0.388	Stabilizing	1.0	D	0.73	deleterious	None	None	None	None	N
D/N	0.1197	likely_benign	0.1042	benign	0.029	Stabilizing	0.998	D	0.761	deleterious	N	0.502141125	None	None	N
D/P	0.441	ambiguous	0.3913	ambiguous	0.129	Stabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
D/Q	0.2949	likely_benign	0.2305	benign	0.054	Stabilizing	0.996	D	0.751	deleterious	None	None	None	None	N
D/R	0.4206	ambiguous	0.3331	benign	0.332	Stabilizing	0.996	D	0.727	deleterious	None	None	None	None	N
D/S	0.1359	likely_benign	0.1139	benign	-0.113	Destabilizing	0.987	D	0.692	prob.delet.	None	None	None	None	N
D/T	0.2353	likely_benign	0.187	benign	0.033	Stabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
D/V	0.1651	likely_benign	0.1389	benign	0.129	Stabilizing	0.998	D	0.721	deleterious	N	0.458991159	None	None	N
D/W	0.8883	likely_pathogenic	0.831	pathogenic	-0.137	Destabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	N
D/Y	0.2887	likely_benign	0.2303	benign	-0.003	Destabilizing	1.0	D	0.703	prob.delet.	N	0.498112958	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.