TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33377	100354;100355;100356	chr2:178536980;178536979;178536978	chr2:179401707;179401706;179401705
N2AB	31736	95431;95432;95433	chr2:178536980;178536979;178536978	chr2:179401707;179401706;179401705
N2A	30809	92650;92651;92652	chr2:178536980;178536979;178536978	chr2:179401707;179401706;179401705
N2B	24312	73159;73160;73161	chr2:178536980;178536979;178536978	chr2:179401707;179401706;179401705
Novex-1	24437	73534;73535;73536	chr2:178536980;178536979;178536978	chr2:179401707;179401706;179401705
Novex-2	24504	73735;73736;73737	chr2:178536980;178536979;178536978	chr2:179401707;179401706;179401705
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-130
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.3187
• 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
P/H	None	None	0.975	D	0.605	0.383	0.558147714631	gnomAD-4.0.0	1.59254E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85995E-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
P/A	0.0824	likely_benign	0.0612	benign	-1.586	Destabilizing	0.001	N	0.363	neutral	N	0.487938876	None	None	I
P/C	0.536	ambiguous	0.3697	ambiguous	-1.029	Destabilizing	0.944	D	0.653	neutral	None	None	None	None	I
P/D	0.7953	likely_pathogenic	0.6443	pathogenic	-1.482	Destabilizing	0.388	N	0.451	neutral	None	None	None	None	I
P/E	0.6659	likely_pathogenic	0.4943	ambiguous	-1.52	Destabilizing	0.388	N	0.435	neutral	None	None	None	None	I
P/F	0.6005	likely_pathogenic	0.4526	ambiguous	-1.35	Destabilizing	0.818	D	0.637	neutral	None	None	None	None	I
P/G	0.4045	ambiguous	0.3091	benign	-1.86	Destabilizing	0.116	N	0.522	neutral	None	None	None	None	I
P/H	0.3565	ambiguous	0.2331	benign	-1.301	Destabilizing	0.975	D	0.605	neutral	D	0.527505202	None	None	I
P/I	0.581	likely_pathogenic	0.3897	ambiguous	-0.943	Destabilizing	0.69	D	0.606	neutral	None	None	None	None	I
P/K	0.6959	likely_pathogenic	0.5081	ambiguous	-1.285	Destabilizing	0.388	N	0.445	neutral	None	None	None	None	I
P/L	0.3982	ambiguous	0.2072	benign	-0.943	Destabilizing	0.193	N	0.529	neutral	N	0.507284125	None	None	I
P/M	0.6248	likely_pathogenic	0.4296	ambiguous	-0.663	Destabilizing	0.944	D	0.603	neutral	None	None	None	None	I
P/N	0.6027	likely_pathogenic	0.425	ambiguous	-1.023	Destabilizing	0.69	D	0.579	neutral	None	None	None	None	I
P/Q	0.4247	ambiguous	0.2705	benign	-1.283	Destabilizing	0.818	D	0.537	neutral	None	None	None	None	I
P/R	0.537	ambiguous	0.3372	benign	-0.649	Destabilizing	0.627	D	0.577	neutral	N	0.511514087	None	None	I
P/S	0.1487	likely_benign	0.1017	benign	-1.506	Destabilizing	0.008	N	0.355	neutral	N	0.489686849	None	None	I
P/T	0.1988	likely_benign	0.1249	benign	-1.446	Destabilizing	0.193	N	0.472	neutral	N	0.511767577	None	None	I
P/V	0.4018	ambiguous	0.2616	benign	-1.123	Destabilizing	0.241	N	0.497	neutral	None	None	None	None	I
P/W	0.8481	likely_pathogenic	0.7243	pathogenic	-1.455	Destabilizing	0.981	D	0.671	neutral	None	None	None	None	I
P/Y	0.6079	likely_pathogenic	0.4429	ambiguous	-1.21	Destabilizing	0.932	D	0.636	neutral	None	None	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.