TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16316	49171;49172;49173	chr2:178614568;178614567;178614566	chr2:179479295;179479294;179479293
N2AB	14675	44248;44249;44250	chr2:178614568;178614567;178614566	chr2:179479295;179479294;179479293
N2A	13748	41467;41468;41469	chr2:178614568;178614567;178614566	chr2:179479295;179479294;179479293
N2B	7251	21976;21977;21978	chr2:178614568;178614567;178614566	chr2:179479295;179479294;179479293
Novex-1	7376	22351;22352;22353	chr2:178614568;178614567;178614566	chr2:179479295;179479294;179479293
Novex-2	7443	22552;22553;22554	chr2:178614568;178614567;178614566	chr2:179479295;179479294;179479293
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-110
• Domain position: 55
• Structural Position: 138
• Q(SASA): 0.0829
• 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	None	None	0.998	N	0.694	0.175	0.454987352986	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	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	0.6782	likely_pathogenic	0.7246	pathogenic	-2.124	Highly Destabilizing	0.996	D	0.659	neutral	N	0.440138462	None	None	N
V/C	0.9106	likely_pathogenic	0.9075	pathogenic	-1.967	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.999	pathogenic	-3.091	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/E	0.9958	likely_pathogenic	0.9965	pathogenic	-2.774	Highly Destabilizing	1.0	D	0.848	deleterious	N	0.509471749	None	None	N
V/F	0.5666	likely_pathogenic	0.6329	pathogenic	-1.233	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
V/G	0.9238	likely_pathogenic	0.9285	pathogenic	-2.765	Highly Destabilizing	1.0	D	0.854	deleterious	N	0.509471749	None	None	N
V/H	0.9977	likely_pathogenic	0.9981	pathogenic	-2.791	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/I	0.0855	likely_benign	0.0931	benign	-0.28	Destabilizing	0.971	D	0.569	neutral	None	None	None	None	N
V/K	0.9966	likely_pathogenic	0.9971	pathogenic	-1.844	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/L	0.1848	likely_benign	0.1952	benign	-0.28	Destabilizing	0.275	N	0.361	neutral	N	0.282834124	None	None	N
V/M	0.342	ambiguous	0.4117	ambiguous	-0.613	Destabilizing	0.998	D	0.694	prob.neutral	N	0.447786473	None	None	N
V/N	0.9952	likely_pathogenic	0.9954	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.9968	pathogenic	-0.871	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/Q	0.9936	likely_pathogenic	0.9946	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/R	0.9933	likely_pathogenic	0.9938	pathogenic	-1.985	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/S	0.9758	likely_pathogenic	0.9799	pathogenic	-3.079	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/T	0.9152	likely_pathogenic	0.9269	pathogenic	-2.583	Highly Destabilizing	0.997	D	0.663	neutral	None	None	None	None	N
V/W	0.9959	likely_pathogenic	0.997	pathogenic	-1.847	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/Y	0.9761	likely_pathogenic	0.98	pathogenic	-1.446	Destabilizing	1.0	D	0.76	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.