TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18272	55039;55040;55041	chr2:178602588;178602587;178602586	chr2:179467315;179467314;179467313
N2AB	16631	50116;50117;50118	chr2:178602588;178602587;178602586	chr2:179467315;179467314;179467313
N2A	15704	47335;47336;47337	chr2:178602588;178602587;178602586	chr2:179467315;179467314;179467313
N2B	9207	27844;27845;27846	chr2:178602588;178602587;178602586	chr2:179467315;179467314;179467313
Novex-1	9332	28219;28220;28221	chr2:178602588;178602587;178602586	chr2:179467315;179467314;179467313
Novex-2	9399	28420;28421;28422	chr2:178602588;178602587;178602586	chr2:179467315;179467314;179467313
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-21
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6941
• 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/L	rs892008187	None	0.908	N	0.643	0.237	0.390842690916	gnomAD-4.0.0	7.44476E-07	None	None	None	None	I	None	3.44661E-05	0	None	0	0	None	0	0	0	0	0
P/S	None	None	0.993	N	0.587	0.316	0.252162846088	gnomAD-4.0.0	3.99739E-06	None	None	None	None	I	None	0	4.98703E-05	None	0	0	None	0	0	3.45149E-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	0.1336	likely_benign	0.1024	benign	-0.323	Destabilizing	0.908	D	0.556	neutral	N	0.475073362	None	None	I
P/C	0.524	ambiguous	0.4038	ambiguous	-0.559	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/D	0.8516	likely_pathogenic	0.7574	pathogenic	-0.002	Destabilizing	0.998	D	0.616	neutral	None	None	None	None	I
P/E	0.4863	ambiguous	0.392	ambiguous	-0.129	Destabilizing	0.995	D	0.611	neutral	None	None	None	None	I
P/F	0.6906	likely_pathogenic	0.5478	ambiguous	-0.733	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
P/G	0.6519	likely_pathogenic	0.531	ambiguous	-0.411	Destabilizing	0.995	D	0.585	neutral	None	None	None	None	I
P/H	0.3978	ambiguous	0.2853	benign	-0.093	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
P/I	0.2172	likely_benign	0.1602	benign	-0.251	Destabilizing	0.929	D	0.65	prob.neutral	None	None	None	None	I
P/K	0.3123	likely_benign	0.2483	benign	-0.087	Destabilizing	0.995	D	0.619	neutral	None	None	None	None	I
P/L	0.1318	likely_benign	0.1006	benign	-0.251	Destabilizing	0.908	D	0.643	neutral	N	0.463934548	None	None	I
P/M	0.3929	ambiguous	0.3007	benign	-0.207	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	I
P/N	0.714	likely_pathogenic	0.5797	pathogenic	0.121	Stabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
P/Q	0.26	likely_benign	0.1849	benign	-0.144	Destabilizing	0.998	D	0.584	neutral	N	0.504488378	None	None	I
P/R	0.2312	likely_benign	0.1626	benign	0.348	Stabilizing	0.993	D	0.779	deleterious	N	0.496219492	None	None	I
P/S	0.2873	likely_benign	0.209	benign	-0.246	Destabilizing	0.993	D	0.587	neutral	N	0.488839659	None	None	I
P/T	0.1848	likely_benign	0.1322	benign	-0.275	Destabilizing	0.986	D	0.589	neutral	N	0.514830726	None	None	I
P/V	0.1524	likely_benign	0.1136	benign	-0.242	Destabilizing	0.075	N	0.371	neutral	None	None	None	None	I
P/W	0.8665	likely_pathogenic	0.7547	pathogenic	-0.79	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
P/Y	0.6858	likely_pathogenic	0.551	ambiguous	-0.448	Destabilizing	0.998	D	0.803	deleterious	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.