TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7473	22642;22643;22644	chr2:178722370;178722369;178722368	chr2:179587097;179587096;179587095
N2AB	7156	21691;21692;21693	chr2:178722370;178722369;178722368	chr2:179587097;179587096;179587095
N2A	6229	18910;18911;18912	chr2:178722370;178722369;178722368	chr2:179587097;179587096;179587095
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-59
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2355
• 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/L	None	None	0.792	N	0.545	0.244	0.52186301387	gnomAD-4.0.0	6.84384E-07	None	None	None	None	N	None	2.99007E-05	0	None	0	0	None	0	0	0	0	0
V/M	rs775242103	-0.593	0.999	N	0.545	0.335	None	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
V/M	rs775242103	-0.593	0.999	N	0.545	0.335	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs775242103	-0.593	0.999	N	0.545	0.335	None	gnomAD-4.0.0	5.57877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.62989E-06	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	0.1931	likely_benign	0.2027	benign	-1.639	Destabilizing	0.925	D	0.451	neutral	N	0.485501746	None	None	N
V/C	0.8715	likely_pathogenic	0.8656	pathogenic	-1.311	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
V/D	0.4369	ambiguous	0.4503	ambiguous	-1.909	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
V/E	0.2744	likely_benign	0.2794	benign	-1.885	Destabilizing	0.959	D	0.727	prob.delet.	D	0.531651248	None	None	N
V/F	0.2127	likely_benign	0.2083	benign	-1.299	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/G	0.3898	ambiguous	0.4017	ambiguous	-1.978	Destabilizing	0.995	D	0.741	deleterious	N	0.505910228	None	None	N
V/H	0.6132	likely_pathogenic	0.6328	pathogenic	-1.544	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/I	0.0751	likely_benign	0.0789	benign	-0.791	Destabilizing	0.924	D	0.519	neutral	None	None	None	None	N
V/K	0.4163	ambiguous	0.4431	ambiguous	-1.289	Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
V/L	0.2721	likely_benign	0.2903	benign	-0.791	Destabilizing	0.792	D	0.545	neutral	N	0.520820966	None	None	N
V/M	0.1329	likely_benign	0.1453	benign	-0.697	Destabilizing	0.999	D	0.545	neutral	N	0.51147004	None	None	N
V/N	0.3324	likely_benign	0.3711	ambiguous	-1.197	Destabilizing	0.973	D	0.757	deleterious	None	None	None	None	N
V/P	0.9791	likely_pathogenic	0.9771	pathogenic	-1.041	Destabilizing	0.986	D	0.762	deleterious	None	None	None	None	N
V/Q	0.3447	ambiguous	0.3704	ambiguous	-1.374	Destabilizing	0.997	D	0.763	deleterious	None	None	None	None	N
V/R	0.3748	ambiguous	0.3945	ambiguous	-0.813	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
V/S	0.2473	likely_benign	0.2615	benign	-1.719	Destabilizing	0.754	D	0.435	neutral	None	None	None	None	N
V/T	0.1327	likely_benign	0.1441	benign	-1.587	Destabilizing	0.299	N	0.356	neutral	None	None	None	None	N
V/W	0.8748	likely_pathogenic	0.8612	pathogenic	-1.532	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/Y	0.6274	likely_pathogenic	0.6373	pathogenic	-1.218	Destabilizing	1.0	D	0.712	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.