TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8414	25465;25466;25467	chr2:178717634;178717633;178717632	chr2:179582361;179582360;179582359
N2AB	8097	24514;24515;24516	chr2:178717634;178717633;178717632	chr2:179582361;179582360;179582359
N2A	7170	21733;21734;21735	chr2:178717634;178717633;178717632	chr2:179582361;179582360;179582359
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-69
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2075
• 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/A	rs759822411	-1.805	0.961	N	0.533	0.245	0.675459934904	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
V/A	rs759822411	-1.805	0.961	N	0.533	0.245	0.675459934904	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9964E-07	1.16042E-05	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	0.2394	likely_benign	0.2839	benign	-1.797	Destabilizing	0.961	D	0.533	neutral	N	0.488299676	None	None	N
V/C	0.8685	likely_pathogenic	0.8937	pathogenic	-1.318	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
V/D	0.4878	ambiguous	0.6167	pathogenic	-2.101	Highly Destabilizing	0.377	N	0.522	neutral	None	None	None	None	N
V/E	0.3518	ambiguous	0.4512	ambiguous	-2.047	Highly Destabilizing	0.922	D	0.655	neutral	N	0.515220358	None	None	N
V/F	0.2328	likely_benign	0.2874	benign	-1.299	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
V/G	0.4161	ambiguous	0.5261	ambiguous	-2.17	Highly Destabilizing	0.995	D	0.699	prob.neutral	N	0.493519721	None	None	N
V/H	0.6112	likely_pathogenic	0.7169	pathogenic	-1.749	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/I	0.0731	likely_benign	0.0796	benign	-0.835	Destabilizing	0.902	D	0.539	neutral	N	0.480993141	None	None	N
V/K	0.3995	ambiguous	0.4999	ambiguous	-1.452	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
V/L	0.2901	likely_benign	0.3473	ambiguous	-0.835	Destabilizing	0.792	D	0.537	neutral	N	0.503581999	None	None	N
V/M	0.1463	likely_benign	0.1753	benign	-0.711	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	N
V/N	0.3619	ambiguous	0.4795	ambiguous	-1.384	Destabilizing	0.973	D	0.752	deleterious	None	None	None	None	N
V/P	0.9785	likely_pathogenic	0.9853	pathogenic	-1.124	Destabilizing	0.995	D	0.738	prob.delet.	None	None	None	None	N
V/Q	0.3933	ambiguous	0.4791	ambiguous	-1.512	Destabilizing	0.997	D	0.746	deleterious	None	None	None	None	N
V/R	0.3657	ambiguous	0.4572	ambiguous	-0.986	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
V/S	0.2886	likely_benign	0.3839	ambiguous	-1.92	Destabilizing	0.975	D	0.655	neutral	None	None	None	None	N
V/T	0.1619	likely_benign	0.192	benign	-1.758	Destabilizing	0.299	N	0.385	neutral	None	None	None	None	N
V/W	0.8634	likely_pathogenic	0.9111	pathogenic	-1.594	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/Y	0.6167	likely_pathogenic	0.697	pathogenic	-1.289	Destabilizing	1.0	D	0.729	prob.delet.	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.