TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8339	25240;25241;25242	chr2:178717991;178717990;178717989	chr2:179582718;179582717;179582716
N2AB	8022	24289;24290;24291	chr2:178717991;178717990;178717989	chr2:179582718;179582717;179582716
N2A	7095	21508;21509;21510	chr2:178717991;178717990;178717989	chr2:179582718;179582717;179582716
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-68
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.3546
• 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
D/E	rs1283273345	-0.57	None	N	0.082	0.171	0.0297737177859	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/E	rs1283273345	-0.57	None	N	0.082	0.171	0.0297737177859	gnomAD-4.0.0	4.77458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57716E-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
D/A	0.1816	likely_benign	0.2239	benign	-0.417	Destabilizing	None	N	0.203	neutral	N	0.422350269	None	None	N
D/C	0.6969	likely_pathogenic	0.8087	pathogenic	-0.205	Destabilizing	0.116	N	0.556	neutral	None	None	None	None	N
D/E	0.0517	likely_benign	0.0511	benign	-0.857	Destabilizing	None	N	0.082	neutral	N	0.358010789	None	None	N
D/F	0.5923	likely_pathogenic	0.6927	pathogenic	-0.661	Destabilizing	0.051	N	0.479	neutral	None	None	None	None	N
D/G	0.243	likely_benign	0.295	benign	-0.714	Destabilizing	0.001	N	0.193	neutral	N	0.457233634	None	None	N
D/H	0.3013	likely_benign	0.3998	ambiguous	-1.013	Destabilizing	0.013	N	0.412	neutral	N	0.43460749	None	None	N
D/I	0.2948	likely_benign	0.377	ambiguous	0.346	Stabilizing	0.003	N	0.434	neutral	None	None	None	None	N
D/K	0.2762	likely_benign	0.3694	ambiguous	-0.348	Destabilizing	None	N	0.181	neutral	None	None	None	None	N
D/L	0.3798	ambiguous	0.4789	ambiguous	0.346	Stabilizing	0.001	N	0.31	neutral	None	None	None	None	N
D/M	0.4938	ambiguous	0.5919	pathogenic	0.789	Stabilizing	0.116	N	0.527	neutral	None	None	None	None	N
D/N	0.1202	likely_benign	0.1509	benign	-0.575	Destabilizing	0.001	N	0.173	neutral	N	0.419542037	None	None	N
D/P	0.9701	likely_pathogenic	0.9869	pathogenic	0.116	Stabilizing	0.003	N	0.287	neutral	None	None	None	None	N
D/Q	0.189	likely_benign	0.2469	benign	-0.499	Destabilizing	None	N	0.179	neutral	None	None	None	None	N
D/R	0.3727	ambiguous	0.4919	ambiguous	-0.407	Destabilizing	None	N	0.201	neutral	None	None	None	None	N
D/S	0.1237	likely_benign	0.1548	benign	-0.867	Destabilizing	None	N	0.107	neutral	None	None	None	None	N
D/T	0.1848	likely_benign	0.2427	benign	-0.621	Destabilizing	0.001	N	0.191	neutral	None	None	None	None	N
D/V	0.1701	likely_benign	0.2154	benign	0.116	Stabilizing	0.001	N	0.33	neutral	N	0.381293081	None	None	N
D/W	0.8494	likely_pathogenic	0.92	pathogenic	-0.716	Destabilizing	0.316	N	0.516	neutral	None	None	None	None	N
D/Y	0.2964	likely_benign	0.3854	ambiguous	-0.458	Destabilizing	0.039	N	0.46	neutral	N	0.47195237	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.