TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6611	20056;20057;20058	chr2:178727747;178727746;178727745	chr2:179592474;179592473;179592472
N2AB	6294	19105;19106;19107	chr2:178727747;178727746;178727745	chr2:179592474;179592473;179592472
N2A	5367	16324;16325;16326	chr2:178727747;178727746;178727745	chr2:179592474;179592473;179592472
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-50
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.8552
• 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
D/G	None	None	0.006	N	0.315	0.146	0.0762999501168	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/N	None	None	0.864	N	0.462	0.236	0.124217242631	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.1172	likely_benign	0.1279	benign	-0.201	Destabilizing	0.477	N	0.423	neutral	N	0.461732502	None	None	I
D/C	0.481	ambiguous	0.5302	ambiguous	-0.16	Destabilizing	0.995	D	0.569	neutral	None	None	None	None	I
D/E	0.1262	likely_benign	0.1432	benign	-0.289	Destabilizing	0.006	N	0.301	neutral	N	0.508194732	None	None	I
D/F	0.5093	ambiguous	0.5402	ambiguous	-0.065	Destabilizing	0.995	D	0.517	neutral	None	None	None	None	I
D/G	0.0875	likely_benign	0.0898	benign	-0.376	Destabilizing	0.006	N	0.315	neutral	N	0.39921068	None	None	I
D/H	0.1817	likely_benign	0.2025	benign	0.388	Stabilizing	0.98	D	0.445	neutral	N	0.491700041	None	None	I
D/I	0.3051	likely_benign	0.3472	ambiguous	0.209	Stabilizing	0.945	D	0.546	neutral	None	None	None	None	I
D/K	0.2018	likely_benign	0.2144	benign	0.354	Stabilizing	0.809	D	0.459	neutral	None	None	None	None	I
D/L	0.3429	ambiguous	0.3718	ambiguous	0.209	Stabilizing	0.894	D	0.54	neutral	None	None	None	None	I
D/M	0.4474	ambiguous	0.5013	ambiguous	0.128	Stabilizing	0.995	D	0.543	neutral	None	None	None	None	I
D/N	0.0672	likely_benign	0.0721	benign	-0.043	Destabilizing	0.864	D	0.462	neutral	N	0.49033969	None	None	I
D/P	0.6332	likely_pathogenic	0.6427	pathogenic	0.093	Stabilizing	0.945	D	0.471	neutral	None	None	None	None	I
D/Q	0.2188	likely_benign	0.2454	benign	None	Stabilizing	0.809	D	0.477	neutral	None	None	None	None	I
D/R	0.2253	likely_benign	0.237	benign	0.639	Stabilizing	0.894	D	0.445	neutral	None	None	None	None	I
D/S	0.0834	likely_benign	0.0923	benign	-0.132	Destabilizing	0.547	D	0.425	neutral	None	None	None	None	I
D/T	0.1558	likely_benign	0.1777	benign	0.016	Stabilizing	0.894	D	0.471	neutral	None	None	None	None	I
D/V	0.2029	likely_benign	0.2281	benign	0.093	Stabilizing	0.864	D	0.556	neutral	N	0.49220702	None	None	I
D/W	0.8095	likely_pathogenic	0.8265	pathogenic	0.077	Stabilizing	0.995	D	0.552	neutral	None	None	None	None	I
D/Y	0.21	likely_benign	0.2245	benign	0.182	Stabilizing	0.993	D	0.523	neutral	N	0.480597225	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.