TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27187	81784;81785;81786	chr2:178564573;178564572;178564571	chr2:179429300;179429299;179429298
N2AB	25546	76861;76862;76863	chr2:178564573;178564572;178564571	chr2:179429300;179429299;179429298
N2A	24619	74080;74081;74082	chr2:178564573;178564572;178564571	chr2:179429300;179429299;179429298
N2B	18122	54589;54590;54591	chr2:178564573;178564572;178564571	chr2:179429300;179429299;179429298
Novex-1	18247	54964;54965;54966	chr2:178564573;178564572;178564571	chr2:179429300;179429299;179429298
Novex-2	18314	55165;55166;55167	chr2:178564573;178564572;178564571	chr2:179429300;179429299;179429298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-86
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1184
• 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
V/F	rs764117771	-1.615	0.864	D	0.821	0.418	0.746452135184	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/F	rs764117771	-1.615	0.864	D	0.821	0.418	0.746452135184	gnomAD-4.0.0	4.79063E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	4.49771E-06	0	1.65722E-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
V/A	0.7384	likely_pathogenic	0.7084	pathogenic	-2.243	Highly Destabilizing	0.645	D	0.561	neutral	N	0.506515156	None	None	N
V/C	0.901	likely_pathogenic	0.8952	pathogenic	-2.201	Highly Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9961	pathogenic	-2.952	Highly Destabilizing	0.928	D	0.843	deleterious	D	0.550452211	None	None	N
V/E	0.9914	likely_pathogenic	0.9885	pathogenic	-2.648	Highly Destabilizing	0.981	D	0.823	deleterious	None	None	None	None	N
V/F	0.7858	likely_pathogenic	0.7415	pathogenic	-1.346	Destabilizing	0.864	D	0.821	deleterious	D	0.531080508	None	None	N
V/G	0.9367	likely_pathogenic	0.9237	pathogenic	-2.85	Highly Destabilizing	0.928	D	0.831	deleterious	D	0.527486111	None	None	N
V/H	0.9966	likely_pathogenic	0.9954	pathogenic	-2.721	Highly Destabilizing	0.995	D	0.847	deleterious	None	None	None	None	N
V/I	0.0728	likely_benign	0.0714	benign	-0.494	Destabilizing	0.006	N	0.195	neutral	N	0.480189772	None	None	N
V/K	0.9925	likely_pathogenic	0.9906	pathogenic	-1.71	Destabilizing	0.945	D	0.823	deleterious	None	None	None	None	N
V/L	0.504	ambiguous	0.4769	ambiguous	-0.494	Destabilizing	0.114	N	0.485	neutral	N	0.470746447	None	None	N
V/M	0.4943	ambiguous	0.4569	ambiguous	-0.992	Destabilizing	0.894	D	0.735	prob.delet.	None	None	None	None	N
V/N	0.9903	likely_pathogenic	0.9855	pathogenic	-2.332	Highly Destabilizing	0.981	D	0.867	deleterious	None	None	None	None	N
V/P	0.9964	likely_pathogenic	0.9947	pathogenic	-1.056	Destabilizing	0.981	D	0.841	deleterious	None	None	None	None	N
V/Q	0.9877	likely_pathogenic	0.9843	pathogenic	-2.002	Highly Destabilizing	0.981	D	0.851	deleterious	None	None	None	None	N
V/R	0.9857	likely_pathogenic	0.9825	pathogenic	-1.83	Destabilizing	0.945	D	0.867	deleterious	None	None	None	None	N
V/S	0.9526	likely_pathogenic	0.9369	pathogenic	-2.952	Highly Destabilizing	0.945	D	0.813	deleterious	None	None	None	None	N
V/T	0.8632	likely_pathogenic	0.8282	pathogenic	-2.475	Highly Destabilizing	0.707	D	0.631	neutral	None	None	None	None	N
V/W	0.9956	likely_pathogenic	0.9942	pathogenic	-1.815	Destabilizing	0.995	D	0.821	deleterious	None	None	None	None	N
V/Y	0.9777	likely_pathogenic	0.9715	pathogenic	-1.483	Destabilizing	0.945	D	0.825	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.