TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17644	53155;53156;53157	chr2:178607857;178607856;178607855	chr2:179472584;179472583;179472582
N2AB	16003	48232;48233;48234	chr2:178607857;178607856;178607855	chr2:179472584;179472583;179472582
N2A	15076	45451;45452;45453	chr2:178607857;178607856;178607855	chr2:179472584;179472583;179472582
N2B	8579	25960;25961;25962	chr2:178607857;178607856;178607855	chr2:179472584;179472583;179472582
Novex-1	8704	26335;26336;26337	chr2:178607857;178607856;178607855	chr2:179472584;179472583;179472582
Novex-2	8771	26536;26537;26538	chr2:178607857;178607856;178607855	chr2:179472584;179472583;179472582
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: Fn3-16
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.1088
• 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/G	rs1490004465	-3.279	1.0	D	0.873	0.857	0.895584942453	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
V/G	rs1490004465	-3.279	1.0	D	0.873	0.857	0.895584942453	gnomAD-4.0.0	3.18555E-06	None	None	None	None	N	None	0	0	None	0	5.56545E-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	0.8786	likely_pathogenic	0.8897	pathogenic	-2.493	Highly Destabilizing	0.999	D	0.649	neutral	D	0.541123136	None	None	N
V/C	0.9733	likely_pathogenic	0.9736	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/D	0.9976	likely_pathogenic	0.9986	pathogenic	-3.443	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/E	0.9939	likely_pathogenic	0.9956	pathogenic	-3.155	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.624376043	None	None	N
V/F	0.9399	likely_pathogenic	0.9334	pathogenic	-1.275	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/G	0.9322	likely_pathogenic	0.9476	pathogenic	-3.043	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.624376043	None	None	N
V/H	0.999	likely_pathogenic	0.9991	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/I	0.1291	likely_benign	0.1135	benign	-0.89	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
V/K	0.9964	likely_pathogenic	0.9971	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/L	0.8566	likely_pathogenic	0.8429	pathogenic	-0.89	Destabilizing	0.997	D	0.661	neutral	N	0.517646375	None	None	N
V/M	0.9141	likely_pathogenic	0.8998	pathogenic	-1.281	Destabilizing	1.0	D	0.743	deleterious	D	0.546149565	None	None	N
V/N	0.9938	likely_pathogenic	0.9953	pathogenic	-2.616	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/P	0.9946	likely_pathogenic	0.9952	pathogenic	-1.408	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/Q	0.9946	likely_pathogenic	0.9954	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/R	0.9909	likely_pathogenic	0.9928	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/S	0.9714	likely_pathogenic	0.9779	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/T	0.943	likely_pathogenic	0.953	pathogenic	-2.675	Highly Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9992	pathogenic	-1.858	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9956	likely_pathogenic	0.995	pathogenic	-1.607	Destabilizing	1.0	D	0.791	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.