TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26985	81178;81179;81180	chr2:178565179;178565178;178565177	chr2:179429906;179429905;179429904
N2AB	25344	76255;76256;76257	chr2:178565179;178565178;178565177	chr2:179429906;179429905;179429904
N2A	24417	73474;73475;73476	chr2:178565179;178565178;178565177	chr2:179429906;179429905;179429904
N2B	17920	53983;53984;53985	chr2:178565179;178565178;178565177	chr2:179429906;179429905;179429904
Novex-1	18045	54358;54359;54360	chr2:178565179;178565178;178565177	chr2:179429906;179429905;179429904
Novex-2	18112	54559;54560;54561	chr2:178565179;178565178;178565177	chr2:179429906;179429905;179429904
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-84
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.2886
• 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	None	None	0.942	N	0.747	0.324	0.662129232514	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	0.4888	ambiguous	0.4249	ambiguous	-1.516	Destabilizing	0.822	D	0.439	neutral	N	0.486438527	None	None	N
V/C	0.8487	likely_pathogenic	0.8144	pathogenic	-1.097	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
V/D	0.8724	likely_pathogenic	0.7997	pathogenic	-1.506	Destabilizing	0.99	D	0.827	deleterious	N	0.520609576	None	None	N
V/E	0.7107	likely_pathogenic	0.6034	pathogenic	-1.361	Destabilizing	0.993	D	0.769	deleterious	None	None	None	None	N
V/F	0.4158	ambiguous	0.3474	ambiguous	-0.867	Destabilizing	0.942	D	0.747	deleterious	N	0.482047662	None	None	N
V/G	0.6469	likely_pathogenic	0.5978	pathogenic	-1.972	Destabilizing	0.971	D	0.808	deleterious	N	0.513229743	None	None	N
V/H	0.8982	likely_pathogenic	0.8379	pathogenic	-1.715	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
V/I	0.0666	likely_benign	0.064	benign	-0.299	Destabilizing	0.014	N	0.21	neutral	N	0.475325457	None	None	N
V/K	0.7233	likely_pathogenic	0.6186	pathogenic	-1.189	Destabilizing	0.978	D	0.772	deleterious	None	None	None	None	N
V/L	0.3464	ambiguous	0.2812	benign	-0.299	Destabilizing	0.247	N	0.327	neutral	N	0.485424569	None	None	N
V/M	0.256	likely_benign	0.2036	benign	-0.402	Destabilizing	0.956	D	0.65	neutral	None	None	None	None	N
V/N	0.7275	likely_pathogenic	0.6084	pathogenic	-1.277	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
V/P	0.9404	likely_pathogenic	0.9176	pathogenic	-0.672	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
V/Q	0.7317	likely_pathogenic	0.6086	pathogenic	-1.206	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/R	0.7183	likely_pathogenic	0.619	pathogenic	-1.017	Destabilizing	0.978	D	0.817	deleterious	None	None	None	None	N
V/S	0.6456	likely_pathogenic	0.5518	ambiguous	-1.906	Destabilizing	0.978	D	0.765	deleterious	None	None	None	None	N
V/T	0.4625	ambiguous	0.3774	ambiguous	-1.63	Destabilizing	0.86	D	0.54	neutral	None	None	None	None	N
V/W	0.9537	likely_pathogenic	0.9335	pathogenic	-1.285	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
V/Y	0.7901	likely_pathogenic	0.7281	pathogenic	-0.874	Destabilizing	0.978	D	0.765	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.