TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17937	54034;54035;54036	chr2:178605486;178605485;178605484	chr2:179470213;179470212;179470211
N2AB	16296	49111;49112;49113	chr2:178605486;178605485;178605484	chr2:179470213;179470212;179470211
N2A	15369	46330;46331;46332	chr2:178605486;178605485;178605484	chr2:179470213;179470212;179470211
N2B	8872	26839;26840;26841	chr2:178605486;178605485;178605484	chr2:179470213;179470212;179470211
Novex-1	8997	27214;27215;27216	chr2:178605486;178605485;178605484	chr2:179470213;179470212;179470211
Novex-2	9064	27415;27416;27417	chr2:178605486;178605485;178605484	chr2:179470213;179470212;179470211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-18
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0787
• 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/D	rs1559723150	None	0.966	D	0.839	0.761	0.901659094074	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66611E-04
V/D	rs1559723150	None	0.966	D	0.839	0.761	0.901659094074	gnomAD-4.0.0	1.59467E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03232E-05

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	0.6812	likely_pathogenic	0.7126	pathogenic	-2.54	Highly Destabilizing	0.005	N	0.307	neutral	N	0.517916773	None	None	N
V/C	0.9066	likely_pathogenic	0.9116	pathogenic	-1.995	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9985	pathogenic	-3.543	Highly Destabilizing	0.966	D	0.839	deleterious	D	0.620429244	None	None	N
V/E	0.9935	likely_pathogenic	0.9948	pathogenic	-3.245	Highly Destabilizing	0.949	D	0.757	deleterious	None	None	None	None	N
V/F	0.9462	likely_pathogenic	0.955	pathogenic	-1.464	Destabilizing	0.966	D	0.685	prob.neutral	D	0.5612024	None	None	N
V/G	0.8618	likely_pathogenic	0.8886	pathogenic	-3.104	Highly Destabilizing	0.669	D	0.763	deleterious	D	0.620429244	None	None	N
V/H	0.9986	likely_pathogenic	0.999	pathogenic	-2.98	Highly Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
V/I	0.1484	likely_benign	0.1536	benign	-0.895	Destabilizing	0.022	N	0.182	neutral	N	0.507262596	None	None	N
V/K	0.9963	likely_pathogenic	0.9972	pathogenic	-2.14	Highly Destabilizing	0.949	D	0.763	deleterious	None	None	None	None	N
V/L	0.7457	likely_pathogenic	0.7732	pathogenic	-0.895	Destabilizing	0.454	N	0.341	neutral	N	0.498225447	None	None	N
V/M	0.8363	likely_pathogenic	0.8653	pathogenic	-1.149	Destabilizing	0.974	D	0.609	neutral	None	None	None	None	N
V/N	0.9914	likely_pathogenic	0.9929	pathogenic	-2.772	Highly Destabilizing	0.974	D	0.853	deleterious	None	None	None	None	N
V/P	0.9939	likely_pathogenic	0.9922	pathogenic	-1.427	Destabilizing	0.974	D	0.809	deleterious	None	None	None	None	N
V/Q	0.9923	likely_pathogenic	0.9939	pathogenic	-2.449	Highly Destabilizing	0.974	D	0.83	deleterious	None	None	None	None	N
V/R	0.9907	likely_pathogenic	0.9927	pathogenic	-2.118	Highly Destabilizing	0.974	D	0.849	deleterious	None	None	None	None	N
V/S	0.9351	likely_pathogenic	0.947	pathogenic	-3.243	Highly Destabilizing	0.728	D	0.707	prob.neutral	None	None	None	None	N
V/T	0.8733	likely_pathogenic	0.9069	pathogenic	-2.806	Highly Destabilizing	0.842	D	0.547	neutral	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9993	pathogenic	-2.069	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9943	likely_pathogenic	0.9954	pathogenic	-1.785	Destabilizing	0.991	D	0.697	prob.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.