TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3081	9466;9467;9468	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803
N2AB	3081	9466;9467;9468	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803
N2A	3081	9466;9467;9468	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803
N2B	3035	9328;9329;9330	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803
Novex-1	3035	9328;9329;9330	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803
Novex-2	3035	9328;9329;9330	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803
Novex-3	3081	9466;9467;9468	chr2:178768078;178768077;178768076	chr2:179632805;179632804;179632803

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-21
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1395
• 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/I	rs1037728221	None	0.001	N	0.246	0.154	0.210429274316	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1037728221	None	0.001	N	0.246	0.154	0.210429274316	gnomAD-4.0.0	2.56121E-06	None	None	None	None	N	None	1.69102E-05	0	None	0	2.42542E-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
V/A	0.9159	likely_pathogenic	0.9312	pathogenic	-2.476	Highly Destabilizing	0.296	N	0.651	neutral	D	0.533128328	None	None	N
V/C	0.975	likely_pathogenic	0.9873	pathogenic	-1.897	Destabilizing	0.991	D	0.767	deleterious	None	None	None	None	N
V/D	0.997	likely_pathogenic	0.997	pathogenic	-3.187	Highly Destabilizing	0.879	D	0.859	deleterious	D	0.780365303	None	None	N
V/E	0.9915	likely_pathogenic	0.9916	pathogenic	-2.928	Highly Destabilizing	0.906	D	0.819	deleterious	None	None	None	None	N
V/F	0.8434	likely_pathogenic	0.8765	pathogenic	-1.194	Destabilizing	0.782	D	0.799	deleterious	D	0.655986275	None	None	N
V/G	0.9487	likely_pathogenic	0.951	pathogenic	-2.995	Highly Destabilizing	0.879	D	0.848	deleterious	D	0.780365303	None	None	N
V/H	0.9978	likely_pathogenic	0.9984	pathogenic	-2.673	Highly Destabilizing	0.991	D	0.847	deleterious	None	None	None	None	N
V/I	0.1102	likely_benign	0.1153	benign	-0.97	Destabilizing	0.001	N	0.246	neutral	N	0.516858502	None	None	N
V/K	0.9946	likely_pathogenic	0.995	pathogenic	-1.867	Destabilizing	0.906	D	0.821	deleterious	None	None	None	None	N
V/L	0.3914	ambiguous	0.5578	ambiguous	-0.97	Destabilizing	0.001	N	0.321	neutral	D	0.52977745	None	None	N
V/M	0.5937	likely_pathogenic	0.7138	pathogenic	-1.218	Destabilizing	0.826	D	0.707	prob.neutral	None	None	None	None	N
V/N	0.9886	likely_pathogenic	0.9895	pathogenic	-2.34	Highly Destabilizing	0.967	D	0.852	deleterious	None	None	None	None	N
V/P	0.9968	likely_pathogenic	0.9965	pathogenic	-1.455	Destabilizing	0.967	D	0.822	deleterious	None	None	None	None	N
V/Q	0.9932	likely_pathogenic	0.9946	pathogenic	-2.073	Highly Destabilizing	0.967	D	0.811	deleterious	None	None	None	None	N
V/R	0.9926	likely_pathogenic	0.9932	pathogenic	-1.802	Destabilizing	0.906	D	0.856	deleterious	None	None	None	None	N
V/S	0.9774	likely_pathogenic	0.9803	pathogenic	-2.86	Highly Destabilizing	0.906	D	0.815	deleterious	None	None	None	None	N
V/T	0.8814	likely_pathogenic	0.9117	pathogenic	-2.477	Highly Destabilizing	0.575	D	0.679	prob.neutral	None	None	None	None	N
V/W	0.9979	likely_pathogenic	0.9986	pathogenic	-1.74	Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9894	likely_pathogenic	0.9917	pathogenic	-1.529	Destabilizing	0.906	D	0.794	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.