TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31261	94006;94007;94008	chr2:178547845;178547844;178547843	chr2:179412572;179412571;179412570
N2AB	29620	89083;89084;89085	chr2:178547845;178547844;178547843	chr2:179412572;179412571;179412570
N2A	28693	86302;86303;86304	chr2:178547845;178547844;178547843	chr2:179412572;179412571;179412570
N2B	22196	66811;66812;66813	chr2:178547845;178547844;178547843	chr2:179412572;179412571;179412570
Novex-1	22321	67186;67187;67188	chr2:178547845;178547844;178547843	chr2:179412572;179412571;179412570
Novex-2	22388	67387;67388;67389	chr2:178547845;178547844;178547843	chr2:179412572;179412571;179412570
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Ig-151
• Domain position: 44
• Structural Position: 115
• Q(SASA): 0.3907
• 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
R/Q	rs755974993	-0.4	1.0	N	0.667	0.371	0.246773566709	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/Q	rs755974993	-0.4	1.0	N	0.667	0.371	0.246773566709	gnomAD-4.0.0	4.78932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39657E-06	1.15934E-05	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
R/A	0.8601	likely_pathogenic	0.9328	pathogenic	-0.634	Destabilizing	0.999	D	0.534	neutral	None	None	None	None	N
R/C	0.5578	ambiguous	0.6833	pathogenic	-0.509	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/D	0.9211	likely_pathogenic	0.9534	pathogenic	-0.03	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
R/E	0.7716	likely_pathogenic	0.8549	pathogenic	0.088	Stabilizing	0.999	D	0.569	neutral	None	None	None	None	N
R/F	0.9235	likely_pathogenic	0.9593	pathogenic	-0.498	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
R/G	0.7951	likely_pathogenic	0.8892	pathogenic	-0.947	Destabilizing	1.0	D	0.659	neutral	N	0.472980811	None	None	N
R/H	0.2629	likely_benign	0.3393	benign	-1.321	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
R/I	0.7587	likely_pathogenic	0.8574	pathogenic	0.201	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
R/K	0.3557	ambiguous	0.4248	ambiguous	-0.688	Destabilizing	0.998	D	0.445	neutral	None	None	None	None	N
R/L	0.7087	likely_pathogenic	0.826	pathogenic	0.201	Stabilizing	1.0	D	0.659	neutral	N	0.496364985	None	None	N
R/M	0.7709	likely_pathogenic	0.8722	pathogenic	-0.103	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
R/N	0.8932	likely_pathogenic	0.9318	pathogenic	-0.134	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
R/P	0.9547	likely_pathogenic	0.9782	pathogenic	-0.056	Destabilizing	1.0	D	0.623	neutral	N	0.497125453	None	None	N
R/Q	0.3105	likely_benign	0.3744	ambiguous	-0.29	Destabilizing	1.0	D	0.667	neutral	N	0.481730223	None	None	N
R/S	0.899	likely_pathogenic	0.9481	pathogenic	-0.837	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
R/T	0.7083	likely_pathogenic	0.8235	pathogenic	-0.54	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/V	0.8511	likely_pathogenic	0.9196	pathogenic	-0.056	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
R/W	0.4977	ambiguous	0.6235	pathogenic	-0.203	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/Y	0.8081	likely_pathogenic	0.8791	pathogenic	0.105	Stabilizing	1.0	D	0.658	neutral	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.