TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16327	49204;49205;49206	chr2:178614535;178614534;178614533	chr2:179479262;179479261;179479260
N2AB	14686	44281;44282;44283	chr2:178614535;178614534;178614533	chr2:179479262;179479261;179479260
N2A	13759	41500;41501;41502	chr2:178614535;178614534;178614533	chr2:179479262;179479261;179479260
N2B	7262	22009;22010;22011	chr2:178614535;178614534;178614533	chr2:179479262;179479261;179479260
Novex-1	7387	22384;22385;22386	chr2:178614535;178614534;178614533	chr2:179479262;179479261;179479260
Novex-2	7454	22585;22586;22587	chr2:178614535;178614534;178614533	chr2:179479262;179479261;179479260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-110
• Domain position: 66
• Structural Position: 152
• Q(SASA): 0.195
• Predicted PPI site: I

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
G/S	None	None	0.63	D	0.464	0.543	0.42538462244	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
G/A	0.4627	ambiguous	0.4149	ambiguous	-0.67	Destabilizing	0.37	N	0.474	neutral	D	0.545983861	None	None	I
G/C	0.8888	likely_pathogenic	0.8949	pathogenic	-0.915	Destabilizing	1.0	D	0.799	deleterious	D	0.818877109	None	None	I
G/D	0.9287	likely_pathogenic	0.9094	pathogenic	-0.935	Destabilizing	0.994	D	0.77	deleterious	D	0.784731337	None	None	I
G/E	0.9737	likely_pathogenic	0.9736	pathogenic	-1.037	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	I
G/F	0.9944	likely_pathogenic	0.9954	pathogenic	-1.16	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
G/H	0.991	likely_pathogenic	0.9911	pathogenic	-1.171	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/I	0.9948	likely_pathogenic	0.996	pathogenic	-0.459	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	I
G/K	0.9925	likely_pathogenic	0.9935	pathogenic	-1.164	Destabilizing	0.995	D	0.776	deleterious	None	None	None	None	I
G/L	0.9878	likely_pathogenic	0.9895	pathogenic	-0.459	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	I
G/M	0.9888	likely_pathogenic	0.9908	pathogenic	-0.358	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/N	0.9548	likely_pathogenic	0.9534	pathogenic	-0.784	Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	I
G/P	0.9995	likely_pathogenic	0.9997	pathogenic	-0.49	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	I
G/Q	0.9713	likely_pathogenic	0.9743	pathogenic	-1.02	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	I
G/R	0.9782	likely_pathogenic	0.9821	pathogenic	-0.783	Destabilizing	0.997	D	0.799	deleterious	D	0.818824461	None	None	I
G/S	0.4893	ambiguous	0.4854	ambiguous	-1.02	Destabilizing	0.63	D	0.464	neutral	D	0.749113279	None	None	I
G/T	0.9372	likely_pathogenic	0.9418	pathogenic	-1.045	Destabilizing	0.967	D	0.778	deleterious	None	None	None	None	I
G/V	0.982	likely_pathogenic	0.9857	pathogenic	-0.49	Destabilizing	0.994	D	0.792	deleterious	D	0.818877109	None	None	I
G/W	0.9938	likely_pathogenic	0.9945	pathogenic	-1.427	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
G/Y	0.9928	likely_pathogenic	0.9937	pathogenic	-1.043	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I

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.