TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8187	24784;24785;24786	chr2:178718547;178718546;178718545	chr2:179583274;179583273;179583272
N2AB	7870	23833;23834;23835	chr2:178718547;178718546;178718545	chr2:179583274;179583273;179583272
N2A	6943	21052;21053;21054	chr2:178718547;178718546;178718545	chr2:179583274;179583273;179583272
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-67
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5326
• 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/R	rs1417467243	0.134	0.942	N	0.636	0.31	0.339074221408	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
P/R	rs1417467243	0.134	0.942	N	0.636	0.31	0.339074221408	gnomAD-4.0.0	4.77506E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57716E-06	0	0
P/S	None	None	0.025	N	0.293	0.093	0.0762999501168	gnomAD-4.0.0	1.59169E-06	None	None	None	None	I	None	0	0	None	0	2.77408E-05	None	0	0	0	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	0.0814	likely_benign	0.0781	benign	-1.212	Destabilizing	0.489	N	0.431	neutral	N	0.452311526	None	None	I
P/C	0.5332	ambiguous	0.5238	ambiguous	-1.03	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	I
P/D	0.4716	ambiguous	0.3959	ambiguous	-0.554	Destabilizing	0.86	D	0.457	neutral	None	None	None	None	I
P/E	0.3516	ambiguous	0.2954	benign	-0.543	Destabilizing	0.86	D	0.457	neutral	None	None	None	None	I
P/F	0.5217	ambiguous	0.4824	ambiguous	-0.794	Destabilizing	0.978	D	0.693	prob.neutral	None	None	None	None	I
P/G	0.2801	likely_benign	0.2601	benign	-1.534	Destabilizing	0.754	D	0.465	neutral	None	None	None	None	I
P/H	0.1869	likely_benign	0.1784	benign	-0.925	Destabilizing	0.992	D	0.624	neutral	N	0.461719275	None	None	I
P/I	0.409	ambiguous	0.3785	ambiguous	-0.439	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	I
P/K	0.2905	likely_benign	0.2528	benign	-0.989	Destabilizing	0.754	D	0.456	neutral	None	None	None	None	I
P/L	0.1676	likely_benign	0.1523	benign	-0.439	Destabilizing	0.942	D	0.603	neutral	N	0.504309065	None	None	I
P/M	0.3756	ambiguous	0.3541	ambiguous	-0.475	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
P/N	0.2771	likely_benign	0.2512	benign	-0.83	Destabilizing	0.915	D	0.549	neutral	None	None	None	None	I
P/Q	0.1707	likely_benign	0.1559	benign	-0.938	Destabilizing	0.956	D	0.531	neutral	None	None	None	None	I
P/R	0.1804	likely_benign	0.1578	benign	-0.536	Destabilizing	0.942	D	0.636	neutral	N	0.497863095	None	None	I
P/S	0.0985	likely_benign	0.0937	benign	-1.455	Destabilizing	0.025	N	0.293	neutral	N	0.415705859	None	None	I
P/T	0.1081	likely_benign	0.1046	benign	-1.318	Destabilizing	0.698	D	0.421	neutral	N	0.47379137	None	None	I
P/V	0.2739	likely_benign	0.2531	benign	-0.66	Destabilizing	0.956	D	0.541	neutral	None	None	None	None	I
P/W	0.6962	likely_pathogenic	0.6446	pathogenic	-0.934	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	I
P/Y	0.4665	ambiguous	0.44	ambiguous	-0.645	Destabilizing	0.993	D	0.693	prob.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.