TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18934	57025;57026;57027	chr2:178598910;178598909;178598908	chr2:179463637;179463636;179463635
N2AB	17293	52102;52103;52104	chr2:178598910;178598909;178598908	chr2:179463637;179463636;179463635
N2A	16366	49321;49322;49323	chr2:178598910;178598909;178598908	chr2:179463637;179463636;179463635
N2B	9869	29830;29831;29832	chr2:178598910;178598909;178598908	chr2:179463637;179463636;179463635
Novex-1	9994	30205;30206;30207	chr2:178598910;178598909;178598908	chr2:179463637;179463636;179463635
Novex-2	10061	30406;30407;30408	chr2:178598910;178598909;178598908	chr2:179463637;179463636;179463635
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: Fn3-25
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2186
• 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/L	rs772344497	-0.334	0.898	N	0.426	0.138	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	1.65865E-04	0	None	0	0	None	0	None	0	0	0
V/L	rs772344497	-0.334	0.898	N	0.426	0.138	None	gnomAD-3.1.2	4.61E-05	None	None	None	None	I	None	1.69074E-04	0	0	0	0	None	0	0	0	0	0
V/L	rs772344497	-0.334	0.898	N	0.426	0.138	None	gnomAD-4.0.0	1.28221E-05	None	None	None	None	I	None	1.69325E-04	0	None	0	0	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	0.4511	ambiguous	0.4303	ambiguous	-1.715	Destabilizing	0.977	D	0.498	neutral	N	0.47442138	None	None	I
V/C	0.8017	likely_pathogenic	0.7804	pathogenic	-1.047	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
V/D	0.9812	likely_pathogenic	0.9761	pathogenic	-1.841	Destabilizing	0.999	D	0.847	deleterious	N	0.508262084	None	None	I
V/E	0.9127	likely_pathogenic	0.9122	pathogenic	-1.723	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	I
V/F	0.7184	likely_pathogenic	0.7023	pathogenic	-1.154	Destabilizing	0.993	D	0.839	deleterious	N	0.474456203	None	None	I
V/G	0.7859	likely_pathogenic	0.7052	pathogenic	-2.143	Highly Destabilizing	0.999	D	0.821	deleterious	N	0.500121783	None	None	I
V/H	0.977	likely_pathogenic	0.9731	pathogenic	-1.691	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/I	0.0945	likely_benign	0.1213	benign	-0.58	Destabilizing	0.117	N	0.335	neutral	N	0.492313708	None	None	I
V/K	0.9583	likely_pathogenic	0.9542	pathogenic	-1.472	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	I
V/L	0.5389	ambiguous	0.5336	ambiguous	-0.58	Destabilizing	0.898	D	0.426	neutral	N	0.504896216	None	None	I
V/M	0.4681	ambiguous	0.5383	ambiguous	-0.412	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
V/N	0.9156	likely_pathogenic	0.9067	pathogenic	-1.531	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	I
V/P	0.9743	likely_pathogenic	0.9668	pathogenic	-0.927	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
V/Q	0.9069	likely_pathogenic	0.8982	pathogenic	-1.53	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	I
V/R	0.9454	likely_pathogenic	0.9337	pathogenic	-1.096	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	I
V/S	0.7881	likely_pathogenic	0.7558	pathogenic	-2.092	Highly Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	I
V/T	0.6692	likely_pathogenic	0.6619	pathogenic	-1.842	Destabilizing	0.983	D	0.612	neutral	None	None	None	None	I
V/W	0.9901	likely_pathogenic	0.9893	pathogenic	-1.523	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
V/Y	0.9551	likely_pathogenic	0.9492	pathogenic	-1.145	Destabilizing	0.999	D	0.845	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.