TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20168	60727;60728;60729	chr2:178591223;178591222;178591221	chr2:179455950;179455949;179455948
N2AB	18527	55804;55805;55806	chr2:178591223;178591222;178591221	chr2:179455950;179455949;179455948
N2A	17600	53023;53024;53025	chr2:178591223;178591222;178591221	chr2:179455950;179455949;179455948
N2B	11103	33532;33533;33534	chr2:178591223;178591222;178591221	chr2:179455950;179455949;179455948
Novex-1	11228	33907;33908;33909	chr2:178591223;178591222;178591221	chr2:179455950;179455949;179455948
Novex-2	11295	34108;34109;34110	chr2:178591223;178591222;178591221	chr2:179455950;179455949;179455948
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: Ig-120
• Domain position: 89
• Structural Position: 177
• Q(SASA): 0.3162
• 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	rs2050126636	None	0.997	D	0.759	0.597	0.783601265864	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs2050126636	None	0.997	D	0.759	0.597	0.783601265864	gnomAD-4.0.0	2.56356E-06	None	None	None	None	N	None	1.69256E-05	0	None	0	0	None	0	0	2.39415E-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	0.928	likely_pathogenic	0.9519	pathogenic	-1.887	Destabilizing	0.999	D	0.75	deleterious	D	0.623858122	None	None	N
V/C	0.9877	likely_pathogenic	0.991	pathogenic	-1.852	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9993	pathogenic	-2.813	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.640482896	None	None	N
V/E	0.997	likely_pathogenic	0.9979	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/F	0.9709	likely_pathogenic	0.9814	pathogenic	-1.371	Destabilizing	1.0	D	0.871	deleterious	D	0.639877483	None	None	N
V/G	0.9769	likely_pathogenic	0.9851	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.640482896	None	None	N
V/H	0.9992	likely_pathogenic	0.9995	pathogenic	-1.644	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
V/I	0.1183	likely_benign	0.139	benign	-0.978	Destabilizing	0.997	D	0.727	prob.delet.	N	0.515625821	None	None	N
V/K	0.9977	likely_pathogenic	0.9983	pathogenic	-1.58	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/L	0.909	likely_pathogenic	0.9405	pathogenic	-0.978	Destabilizing	0.997	D	0.759	deleterious	D	0.589569193	None	None	N
V/M	0.9008	likely_pathogenic	0.9315	pathogenic	-1.098	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/N	0.9931	likely_pathogenic	0.9954	pathogenic	-1.703	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/P	0.9911	likely_pathogenic	0.9942	pathogenic	-1.253	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/Q	0.9971	likely_pathogenic	0.998	pathogenic	-1.861	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/R	0.9956	likely_pathogenic	0.9967	pathogenic	-1.087	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/S	0.9735	likely_pathogenic	0.9827	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/T	0.9105	likely_pathogenic	0.9342	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
V/W	0.9998	likely_pathogenic	0.9999	pathogenic	-1.63	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/Y	0.9981	likely_pathogenic	0.9988	pathogenic	-1.331	Destabilizing	1.0	D	0.878	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.