TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5518	16777;16778;16779	chr2:178732509;178732508;178732507	chr2:179597236;179597235;179597234
N2AB	5201	15826;15827;15828	chr2:178732509;178732508;178732507	chr2:179597236;179597235;179597234
N2A	4274	13045;13046;13047	chr2:178732509;178732508;178732507	chr2:179597236;179597235;179597234
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-38
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2244
• 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
G/D	None	None	0.071	D	0.607	0.524	0.104622674875	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
G/A	0.2385	likely_benign	0.2624	benign	-0.648	Destabilizing	0.122	N	0.43	neutral	D	0.56564731	None	None	N
G/C	0.5954	likely_pathogenic	0.6863	pathogenic	-0.947	Destabilizing	1.0	D	0.826	deleterious	D	0.651587515	None	None	N
G/D	0.3034	likely_benign	0.4039	ambiguous	-0.518	Destabilizing	0.071	N	0.607	neutral	D	0.62587796	None	None	N
G/E	0.5791	likely_pathogenic	0.6689	pathogenic	-0.585	Destabilizing	0.942	D	0.77	deleterious	None	None	None	None	N
G/F	0.9366	likely_pathogenic	0.9576	pathogenic	-1.073	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
G/H	0.8587	likely_pathogenic	0.9162	pathogenic	-1.17	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/I	0.8855	likely_pathogenic	0.9102	pathogenic	-0.327	Destabilizing	0.996	D	0.823	deleterious	None	None	None	None	N
G/K	0.8652	likely_pathogenic	0.9132	pathogenic	-0.941	Destabilizing	0.991	D	0.788	deleterious	None	None	None	None	N
G/L	0.8519	likely_pathogenic	0.8927	pathogenic	-0.327	Destabilizing	0.991	D	0.815	deleterious	None	None	None	None	N
G/M	0.8706	likely_pathogenic	0.9056	pathogenic	-0.322	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
G/N	0.5869	likely_pathogenic	0.6862	pathogenic	-0.641	Destabilizing	0.991	D	0.708	prob.delet.	None	None	None	None	N
G/P	0.9917	likely_pathogenic	0.9945	pathogenic	-0.394	Destabilizing	0.996	D	0.794	deleterious	None	None	None	None	N
G/Q	0.6927	likely_pathogenic	0.7754	pathogenic	-0.798	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
G/R	0.7456	likely_pathogenic	0.8177	pathogenic	-0.707	Destabilizing	0.994	D	0.799	deleterious	D	0.63536635	None	None	N
G/S	0.1903	likely_benign	0.2263	benign	-0.994	Destabilizing	0.489	N	0.493	neutral	D	0.634962741	None	None	N
G/T	0.5984	likely_pathogenic	0.6543	pathogenic	-0.963	Destabilizing	0.942	D	0.772	deleterious	None	None	None	None	N
G/V	0.7672	likely_pathogenic	0.8083	pathogenic	-0.394	Destabilizing	0.989	D	0.813	deleterious	D	0.606547573	None	None	N
G/W	0.9093	likely_pathogenic	0.9477	pathogenic	-1.366	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/Y	0.8967	likely_pathogenic	0.9358	pathogenic	-0.942	Destabilizing	0.999	D	0.833	deleterious	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.