TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8847	26764;26765;26766	chr2:178714119;178714118;178714117	chr2:179578846;179578845;179578844
N2AB	8530	25813;25814;25815	chr2:178714119;178714118;178714117	chr2:179578846;179578845;179578844
N2A	7603	23032;23033;23034	chr2:178714119;178714118;178714117	chr2:179578846;179578845;179578844
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-74
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1624
• 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
C/G	None	None	0.92	N	0.663	0.287	0.514416127146	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
C/W	None	None	0.999	N	0.659	0.257	0.293502639404	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
C/Y	None	None	0.996	N	0.727	0.339	0.493964856914	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	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
C/A	0.2684	likely_benign	0.2987	benign	-1.721	Destabilizing	0.028	N	0.159	neutral	None	None	None	None	N
C/D	0.939	likely_pathogenic	0.9593	pathogenic	-0.066	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
C/E	0.962	likely_pathogenic	0.9731	pathogenic	0.06	Stabilizing	0.991	D	0.75	deleterious	None	None	None	None	N
C/F	0.2379	likely_benign	0.2805	benign	-1.097	Destabilizing	0.976	D	0.731	prob.delet.	N	0.375822106	None	None	N
C/G	0.2099	likely_benign	0.2602	benign	-2.042	Highly Destabilizing	0.92	D	0.663	neutral	N	0.411166831	None	None	N
C/H	0.7814	likely_pathogenic	0.84	pathogenic	-1.904	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
C/I	0.4125	ambiguous	0.4719	ambiguous	-0.892	Destabilizing	0.884	D	0.616	neutral	None	None	None	None	N
C/K	0.9493	likely_pathogenic	0.9647	pathogenic	-0.717	Destabilizing	0.969	D	0.703	prob.neutral	None	None	None	None	N
C/L	0.4205	ambiguous	0.4886	ambiguous	-0.892	Destabilizing	0.02	N	0.387	neutral	None	None	None	None	N
C/M	0.66	likely_pathogenic	0.7255	pathogenic	0.008	Stabilizing	0.982	D	0.708	prob.delet.	None	None	None	None	N
C/N	0.8166	likely_pathogenic	0.8735	pathogenic	-0.858	Destabilizing	0.997	D	0.749	deleterious	None	None	None	None	N
C/P	0.9762	likely_pathogenic	0.9846	pathogenic	-1.143	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
C/Q	0.8607	likely_pathogenic	0.8976	pathogenic	-0.67	Destabilizing	0.997	D	0.754	deleterious	None	None	None	None	N
C/R	0.7524	likely_pathogenic	0.798	pathogenic	-0.667	Destabilizing	0.988	D	0.755	deleterious	N	0.443489893	None	None	N
C/S	0.3105	likely_benign	0.3889	ambiguous	-1.434	Destabilizing	0.704	D	0.583	neutral	N	0.420421032	None	None	N
C/T	0.5087	ambiguous	0.5642	pathogenic	-1.104	Destabilizing	0.939	D	0.619	neutral	None	None	None	None	N
C/V	0.3212	likely_benign	0.3487	ambiguous	-1.143	Destabilizing	0.759	D	0.549	neutral	None	None	None	None	N
C/W	0.6623	likely_pathogenic	0.756	pathogenic	-1.065	Destabilizing	0.999	D	0.659	neutral	N	0.473466083	None	None	N
C/Y	0.41	ambiguous	0.498	ambiguous	-1.048	Destabilizing	0.996	D	0.727	prob.delet.	N	0.435678486	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.