TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21752	65479;65480;65481	chr2:178584297;178584296;178584295	chr2:179449024;179449023;179449022
N2AB	20111	60556;60557;60558	chr2:178584297;178584296;178584295	chr2:179449024;179449023;179449022
N2A	19184	57775;57776;57777	chr2:178584297;178584296;178584295	chr2:179449024;179449023;179449022
N2B	12687	38284;38285;38286	chr2:178584297;178584296;178584295	chr2:179449024;179449023;179449022
Novex-1	12812	38659;38660;38661	chr2:178584297;178584296;178584295	chr2:179449024;179449023;179449022
Novex-2	12879	38860;38861;38862	chr2:178584297;178584296;178584295	chr2:179449024;179449023;179449022
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: Fn3-45
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.2156
• 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	0.506	N	0.417	0.206	0.568285537894	gnomAD-4.0.0	1.04784E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.37055E-05	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	0.3785	ambiguous	0.2978	benign	-1.519	Destabilizing	0.824	D	0.591	neutral	N	0.477770658	None	None	N
V/C	0.7493	likely_pathogenic	0.7074	pathogenic	-1.139	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
V/D	0.8285	likely_pathogenic	0.752	pathogenic	-1.119	Destabilizing	0.997	D	0.85	deleterious	None	None	None	None	N
V/E	0.6033	likely_pathogenic	0.5147	ambiguous	-1.012	Destabilizing	0.996	D	0.794	deleterious	N	0.489545037	None	None	N
V/F	0.3083	likely_benign	0.2498	benign	-0.901	Destabilizing	0.991	D	0.771	deleterious	None	None	None	None	N
V/G	0.5594	ambiguous	0.4846	ambiguous	-1.943	Destabilizing	0.996	D	0.807	deleterious	N	0.490305506	None	None	N
V/H	0.7923	likely_pathogenic	0.7216	pathogenic	-1.33	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
V/I	0.0958	likely_benign	0.0843	benign	-0.41	Destabilizing	0.06	N	0.207	neutral	N	0.476437391	None	None	N
V/K	0.6271	likely_pathogenic	0.5317	ambiguous	-1.226	Destabilizing	0.997	D	0.801	deleterious	None	None	None	None	N
V/L	0.3379	likely_benign	0.2729	benign	-0.41	Destabilizing	0.506	D	0.417	neutral	N	0.517822654	None	None	N
V/M	0.2308	likely_benign	0.1862	benign	-0.425	Destabilizing	0.991	D	0.651	prob.neutral	None	None	None	None	N
V/N	0.7092	likely_pathogenic	0.6137	pathogenic	-1.275	Destabilizing	0.997	D	0.827	deleterious	None	None	None	None	N
V/P	0.9716	likely_pathogenic	0.9567	pathogenic	-0.746	Destabilizing	0.997	D	0.815	deleterious	None	None	None	None	N
V/Q	0.5001	ambiguous	0.4321	ambiguous	-1.252	Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	N
V/R	0.5318	ambiguous	0.456	ambiguous	-0.887	Destabilizing	0.997	D	0.83	deleterious	None	None	None	None	N
V/S	0.5155	ambiguous	0.4393	ambiguous	-1.942	Destabilizing	0.997	D	0.723	deleterious	None	None	None	None	N
V/T	0.3102	likely_benign	0.2533	benign	-1.689	Destabilizing	0.968	D	0.669	prob.neutral	None	None	None	None	N
V/W	0.9311	likely_pathogenic	0.8903	pathogenic	-1.164	Destabilizing	0.999	D	0.729	deleterious	None	None	None	None	N
V/Y	0.7562	likely_pathogenic	0.6783	pathogenic	-0.819	Destabilizing	0.997	D	0.748	deleterious	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.