TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29990	90193;90194;90195	chr2:178552932;178552931;178552930	chr2:179417659;179417658;179417657
N2AB	28349	85270;85271;85272	chr2:178552932;178552931;178552930	chr2:179417659;179417658;179417657
N2A	27422	82489;82490;82491	chr2:178552932;178552931;178552930	chr2:179417659;179417658;179417657
N2B	20925	62998;62999;63000	chr2:178552932;178552931;178552930	chr2:179417659;179417658;179417657
Novex-1	21050	63373;63374;63375	chr2:178552932;178552931;178552930	chr2:179417659;179417658;179417657
Novex-2	21117	63574;63575;63576	chr2:178552932;178552931;178552930	chr2:179417659;179417658;179417657
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-106
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.1637
• 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
T/I	None	None	0.89	N	0.562	0.338	0.41518383557	gnomAD-4.0.0	6.84257E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	0
T/K	rs1699983035	None	0.89	N	0.562	0.366	0.402899589544	gnomAD-4.0.0	1.36851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79891E-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
T/A	0.0903	likely_benign	0.0894	benign	-0.978	Destabilizing	0.489	N	0.436	neutral	N	0.509871927	None	None	N
T/C	0.3358	likely_benign	0.3371	benign	-0.409	Destabilizing	0.998	D	0.65	neutral	None	None	None	None	N
T/D	0.5956	likely_pathogenic	0.541	ambiguous	-0.147	Destabilizing	0.956	D	0.563	neutral	None	None	None	None	N
T/E	0.5076	ambiguous	0.4771	ambiguous	-0.025	Destabilizing	0.956	D	0.563	neutral	None	None	None	None	N
T/F	0.3883	ambiguous	0.3433	ambiguous	-0.893	Destabilizing	0.956	D	0.699	prob.neutral	None	None	None	None	N
T/G	0.2546	likely_benign	0.2363	benign	-1.331	Destabilizing	0.754	D	0.559	neutral	None	None	None	None	N
T/H	0.3279	likely_benign	0.3013	benign	-1.359	Destabilizing	0.994	D	0.713	prob.delet.	None	None	None	None	N
T/I	0.2335	likely_benign	0.2042	benign	-0.087	Destabilizing	0.89	D	0.562	neutral	N	0.517380345	None	None	N
T/K	0.2636	likely_benign	0.249	benign	-0.23	Destabilizing	0.89	D	0.562	neutral	N	0.498008642	None	None	N
T/L	0.081	likely_benign	0.0749	benign	-0.087	Destabilizing	0.514	D	0.453	neutral	None	None	None	None	N
T/M	0.0991	likely_benign	0.1011	benign	-0.033	Destabilizing	0.559	D	0.422	neutral	None	None	None	None	N
T/N	0.1188	likely_benign	0.1059	benign	-0.588	Destabilizing	0.915	D	0.508	neutral	None	None	None	None	N
T/P	0.0944	likely_benign	0.0911	benign	-0.352	Destabilizing	0.971	D	0.601	neutral	N	0.478512036	None	None	N
T/Q	0.255	likely_benign	0.2493	benign	-0.485	Destabilizing	0.956	D	0.607	neutral	None	None	None	None	N
T/R	0.2123	likely_benign	0.2024	benign	-0.272	Destabilizing	0.942	D	0.6	neutral	N	0.49553988	None	None	N
T/S	0.1249	likely_benign	0.1146	benign	-0.964	Destabilizing	0.058	N	0.506	neutral	N	0.502021114	None	None	N
T/V	0.1642	likely_benign	0.1494	benign	-0.352	Destabilizing	0.754	D	0.429	neutral	None	None	None	None	N
T/W	0.801	likely_pathogenic	0.7678	pathogenic	-0.909	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
T/Y	0.3971	ambiguous	0.355	ambiguous	-0.578	Destabilizing	0.978	D	0.713	prob.delet.	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.