TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19579	58960;58961;58962	chr2:178593473;178593472;178593471	chr2:179458200;179458199;179458198
N2AB	17938	54037;54038;54039	chr2:178593473;178593472;178593471	chr2:179458200;179458199;179458198
N2A	17011	51256;51257;51258	chr2:178593473;178593472;178593471	chr2:179458200;179458199;179458198
N2B	10514	31765;31766;31767	chr2:178593473;178593472;178593471	chr2:179458200;179458199;179458198
Novex-1	10639	32140;32141;32142	chr2:178593473;178593472;178593471	chr2:179458200;179458199;179458198
Novex-2	10706	32341;32342;32343	chr2:178593473;178593472;178593471	chr2:179458200;179458199;179458198
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: Fn3-30
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.8676
• Predicted PPI site: I

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	None	None	0.999	N	0.809	0.516	0.718557029062	gnomAD-4.0.0	1.37633E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.20166E-05	1.66539E-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	0.3023	likely_benign	0.3006	benign	-0.76	Destabilizing	0.997	D	0.523	neutral	N	0.521209676	None	None	I
V/C	0.7621	likely_pathogenic	0.7812	pathogenic	-0.741	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
V/D	0.706	likely_pathogenic	0.703	pathogenic	-0.391	Destabilizing	0.999	D	0.809	deleterious	N	0.498587619	None	None	I
V/E	0.4796	ambiguous	0.4761	ambiguous	-0.499	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
V/F	0.3241	likely_benign	0.3299	benign	-0.991	Destabilizing	0.999	D	0.715	prob.delet.	N	0.491079201	None	None	I
V/G	0.4109	ambiguous	0.4077	ambiguous	-0.909	Destabilizing	0.999	D	0.781	deleterious	N	0.509690435	None	None	I
V/H	0.7356	likely_pathogenic	0.7485	pathogenic	-0.421	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
V/I	0.091	likely_benign	0.0926	benign	-0.512	Destabilizing	0.994	D	0.579	neutral	N	0.509051242	None	None	I
V/K	0.3524	ambiguous	0.3765	ambiguous	-0.432	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
V/L	0.2865	likely_benign	0.3024	benign	-0.512	Destabilizing	0.994	D	0.597	neutral	N	0.470097656	None	None	I
V/M	0.2644	likely_benign	0.2651	benign	-0.361	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	I
V/N	0.5359	ambiguous	0.5407	ambiguous	-0.201	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
V/P	0.3246	likely_benign	0.3449	ambiguous	-0.56	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
V/Q	0.4279	ambiguous	0.4477	ambiguous	-0.502	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
V/R	0.3333	likely_benign	0.3596	ambiguous	0.111	Stabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
V/S	0.434	ambiguous	0.4307	ambiguous	-0.64	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
V/T	0.3029	likely_benign	0.3108	benign	-0.647	Destabilizing	0.998	D	0.707	prob.delet.	None	None	None	None	I
V/W	0.9044	likely_pathogenic	0.9082	pathogenic	-1.014	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
V/Y	0.6864	likely_pathogenic	0.7049	pathogenic	-0.702	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	I

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.