TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7029	21310;21311;21312	chr2:178724290;178724289;178724288	chr2:179589017;179589016;179589015
N2AB	6712	20359;20360;20361	chr2:178724290;178724289;178724288	chr2:179589017;179589016;179589015
N2A	5785	17578;17579;17580	chr2:178724290;178724289;178724288	chr2:179589017;179589016;179589015
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-54
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2028
• 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
S/N	rs1371527659	-0.327	0.961	N	0.557	0.239	0.226586394389	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66168E-04
S/N	rs1371527659	-0.327	0.961	N	0.557	0.239	0.226586394389	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05

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
S/A	0.1156	likely_benign	0.1317	benign	-0.587	Destabilizing	0.931	D	0.54	neutral	None	None	None	None	N
S/C	0.2227	likely_benign	0.2369	benign	-0.531	Destabilizing	1.0	D	0.693	prob.neutral	N	0.510529401	None	None	N
S/D	0.2465	likely_benign	0.2569	benign	-0.091	Destabilizing	0.041	N	0.251	neutral	None	None	None	None	N
S/E	0.5992	likely_pathogenic	0.6068	pathogenic	-0.069	Destabilizing	0.942	D	0.533	neutral	None	None	None	None	N
S/F	0.5024	ambiguous	0.4578	ambiguous	-0.658	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
S/G	0.1627	likely_benign	0.1737	benign	-0.861	Destabilizing	0.071	N	0.263	neutral	N	0.485327616	None	None	N
S/H	0.5649	likely_pathogenic	0.5593	ambiguous	-1.272	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/I	0.3857	ambiguous	0.3631	ambiguous	0.035	Stabilizing	0.998	D	0.766	deleterious	N	0.466815909	None	None	N
S/K	0.8726	likely_pathogenic	0.868	pathogenic	-0.598	Destabilizing	0.97	D	0.582	neutral	None	None	None	None	N
S/L	0.2736	likely_benign	0.2646	benign	0.035	Stabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
S/M	0.3872	ambiguous	0.4024	ambiguous	0.084	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
S/N	0.1978	likely_benign	0.1892	benign	-0.633	Destabilizing	0.961	D	0.557	neutral	N	0.48838326	None	None	N
S/P	0.9756	likely_pathogenic	0.9661	pathogenic	-0.137	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
S/Q	0.6761	likely_pathogenic	0.6828	pathogenic	-0.707	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	N
S/R	0.8308	likely_pathogenic	0.8169	pathogenic	-0.561	Destabilizing	0.994	D	0.729	prob.delet.	N	0.49090349	None	None	N
S/T	0.141	likely_benign	0.139	benign	-0.623	Destabilizing	0.98	D	0.558	neutral	N	0.443400332	None	None	N
S/V	0.3669	ambiguous	0.3584	ambiguous	-0.137	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
S/W	0.6926	likely_pathogenic	0.6554	pathogenic	-0.663	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
S/Y	0.3737	ambiguous	0.3394	benign	-0.37	Destabilizing	0.999	D	0.746	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.