TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14243	42952;42953;42954	chr2:178633632;178633631;178633630	chr2:179498359;179498358;179498357
N2AB	12602	38029;38030;38031	chr2:178633632;178633631;178633630	chr2:179498359;179498358;179498357
N2A	11675	35248;35249;35250	chr2:178633632;178633631;178633630	chr2:179498359;179498358;179498357
N2B	5178	15757;15758;15759	chr2:178633632;178633631;178633630	chr2:179498359;179498358;179498357
Novex-1	5303	16132;16133;16134	chr2:178633632;178633631;178633630	chr2:179498359;179498358;179498357
Novex-2	5370	16333;16334;16335	chr2:178633632;178633631;178633630	chr2:179498359;179498358;179498357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-93
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.3847
• 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/E	None	None	0.782	N	0.538	0.208	0.550005317886	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

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	0.1853	likely_benign	0.1619	benign	-1.443	Destabilizing	0.174	N	0.372	neutral	N	0.504968066	None	None	N
V/C	0.8112	likely_pathogenic	0.7865	pathogenic	-0.922	Destabilizing	0.973	D	0.484	neutral	None	None	None	None	N
V/D	0.4638	ambiguous	0.3866	ambiguous	-1.496	Destabilizing	0.826	D	0.573	neutral	None	None	None	None	N
V/E	0.3348	likely_benign	0.2939	benign	-1.553	Destabilizing	0.782	D	0.538	neutral	N	0.504858086	None	None	N
V/F	0.2435	likely_benign	0.1713	benign	-1.316	Destabilizing	0.826	D	0.465	neutral	None	None	None	None	N
V/G	0.2694	likely_benign	0.2231	benign	-1.699	Destabilizing	0.782	D	0.534	neutral	D	0.592790785	None	None	N
V/H	0.6564	likely_pathogenic	0.6083	pathogenic	-1.204	Destabilizing	0.991	D	0.592	neutral	None	None	None	None	N
V/I	0.0848	likely_benign	0.0784	benign	-0.855	Destabilizing	0.004	N	0.229	neutral	None	None	None	None	N
V/K	0.3194	likely_benign	0.295	benign	-1.171	Destabilizing	0.826	D	0.534	neutral	None	None	None	None	N
V/L	0.2154	likely_benign	0.1897	benign	-0.855	Destabilizing	0.003	N	0.262	neutral	N	0.500876099	None	None	N
V/M	0.1618	likely_benign	0.1322	benign	-0.563	Destabilizing	0.782	D	0.448	neutral	N	0.50574142	None	None	N
V/N	0.2947	likely_benign	0.2676	benign	-0.882	Destabilizing	0.826	D	0.58	neutral	None	None	None	None	N
V/P	0.4975	ambiguous	0.5455	ambiguous	-1.017	Destabilizing	0.906	D	0.558	neutral	None	None	None	None	N
V/Q	0.3259	likely_benign	0.3149	benign	-1.169	Destabilizing	0.906	D	0.567	neutral	None	None	None	None	N
V/R	0.309	likely_benign	0.2647	benign	-0.544	Destabilizing	0.826	D	0.581	neutral	None	None	None	None	N
V/S	0.2235	likely_benign	0.1963	benign	-1.317	Destabilizing	0.404	N	0.477	neutral	None	None	None	None	N
V/T	0.137	likely_benign	0.1319	benign	-1.281	Destabilizing	0.004	N	0.227	neutral	None	None	None	None	N
V/W	0.8574	likely_pathogenic	0.799	pathogenic	-1.423	Destabilizing	0.991	D	0.618	neutral	None	None	None	None	N
V/Y	0.6663	likely_pathogenic	0.5949	pathogenic	-1.166	Destabilizing	0.906	D	0.457	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.