TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8140	24643;24644;24645	chr2:178718782;178718781;178718780	chr2:179583509;179583508;179583507
N2AB	7823	23692;23693;23694	chr2:178718782;178718781;178718780	chr2:179583509;179583508;179583507
N2A	6896	20911;20912;20913	chr2:178718782;178718781;178718780	chr2:179583509;179583508;179583507
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-66
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0836
• 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/M	rs377210838	-1.18	0.978	D	0.753	0.615	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/M	rs377210838	-1.18	0.978	D	0.753	0.615	None	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9948E-07	0	1.65656E-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	0.3484	ambiguous	0.3282	benign	-2.288	Highly Destabilizing	0.928	D	0.527	neutral	N	0.489633257	None	None	N
V/C	0.8944	likely_pathogenic	0.8765	pathogenic	-2.112	Highly Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
V/D	0.9001	likely_pathogenic	0.9	pathogenic	-2.974	Highly Destabilizing	0.997	D	0.776	deleterious	None	None	None	None	N
V/E	0.85	likely_pathogenic	0.8515	pathogenic	-2.806	Highly Destabilizing	0.989	D	0.744	deleterious	D	0.563325087	None	None	N
V/F	0.458	ambiguous	0.4677	ambiguous	-1.461	Destabilizing	0.968	D	0.759	deleterious	None	None	None	None	N
V/G	0.4667	ambiguous	0.4724	ambiguous	-2.776	Highly Destabilizing	0.989	D	0.745	deleterious	D	0.545220832	None	None	N
V/H	0.9543	likely_pathogenic	0.9554	pathogenic	-2.383	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
V/I	0.0936	likely_benign	0.0912	benign	-0.946	Destabilizing	0.778	D	0.514	neutral	None	None	None	None	N
V/K	0.8891	likely_pathogenic	0.8924	pathogenic	-2.017	Highly Destabilizing	0.992	D	0.737	prob.delet.	None	None	None	None	N
V/L	0.3299	likely_benign	0.3066	benign	-0.946	Destabilizing	0.039	N	0.313	neutral	N	0.490334954	None	None	N
V/M	0.3199	likely_benign	0.2906	benign	-1.083	Destabilizing	0.978	D	0.753	deleterious	D	0.536320062	None	None	N
V/N	0.7903	likely_pathogenic	0.7808	pathogenic	-2.266	Highly Destabilizing	0.997	D	0.784	deleterious	None	None	None	None	N
V/P	0.7929	likely_pathogenic	0.828	pathogenic	-1.365	Destabilizing	0.997	D	0.754	deleterious	None	None	None	None	N
V/Q	0.8687	likely_pathogenic	0.8651	pathogenic	-2.21	Highly Destabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
V/R	0.8585	likely_pathogenic	0.8652	pathogenic	-1.673	Destabilizing	0.992	D	0.783	deleterious	None	None	None	None	N
V/S	0.6064	likely_pathogenic	0.584	pathogenic	-2.868	Highly Destabilizing	0.992	D	0.72	prob.delet.	None	None	None	None	N
V/T	0.4271	ambiguous	0.392	ambiguous	-2.567	Highly Destabilizing	0.944	D	0.633	neutral	None	None	None	None	N
V/W	0.9681	likely_pathogenic	0.9691	pathogenic	-1.895	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
V/Y	0.8896	likely_pathogenic	0.8962	pathogenic	-1.58	Destabilizing	0.992	D	0.759	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.