TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19709	59350;59351;59352	chr2:178592994;178592993;178592992	chr2:179457721;179457720;179457719
N2AB	18068	54427;54428;54429	chr2:178592994;178592993;178592992	chr2:179457721;179457720;179457719
N2A	17141	51646;51647;51648	chr2:178592994;178592993;178592992	chr2:179457721;179457720;179457719
N2B	10644	32155;32156;32157	chr2:178592994;178592993;178592992	chr2:179457721;179457720;179457719
Novex-1	10769	32530;32531;32532	chr2:178592994;178592993;178592992	chr2:179457721;179457720;179457719
Novex-2	10836	32731;32732;32733	chr2:178592994;178592993;178592992	chr2:179457721;179457720;179457719
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-31
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5524
• 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/E	None	None	0.379	N	0.476	0.358	0.41337360676	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.3779	ambiguous	0.5019	ambiguous	-0.228	Destabilizing	0.379	N	0.285	neutral	N	0.486512023	None	None	I
G/C	0.4326	ambiguous	0.5553	ambiguous	-0.921	Destabilizing	0.992	D	0.651	neutral	None	None	None	None	I
G/D	0.5374	ambiguous	0.633	pathogenic	-0.472	Destabilizing	0.447	N	0.4	neutral	None	None	None	None	I
G/E	0.5915	likely_pathogenic	0.6793	pathogenic	-0.621	Destabilizing	0.379	N	0.476	neutral	N	0.509655934	None	None	I
G/F	0.8228	likely_pathogenic	0.8836	pathogenic	-0.978	Destabilizing	0.972	D	0.621	neutral	None	None	None	None	I
G/H	0.5363	ambiguous	0.6676	pathogenic	-0.296	Destabilizing	0.92	D	0.601	neutral	None	None	None	None	I
G/I	0.7622	likely_pathogenic	0.8496	pathogenic	-0.495	Destabilizing	0.92	D	0.627	neutral	None	None	None	None	I
G/K	0.4158	ambiguous	0.5624	ambiguous	-0.475	Destabilizing	0.005	N	0.375	neutral	None	None	None	None	I
G/L	0.7151	likely_pathogenic	0.8254	pathogenic	-0.495	Destabilizing	0.85	D	0.596	neutral	None	None	None	None	I
G/M	0.7347	likely_pathogenic	0.8456	pathogenic	-0.575	Destabilizing	0.992	D	0.611	neutral	None	None	None	None	I
G/N	0.3814	ambiguous	0.5518	ambiguous	-0.254	Destabilizing	0.005	N	0.199	neutral	None	None	None	None	I
G/P	0.9768	likely_pathogenic	0.9788	pathogenic	-0.384	Destabilizing	0.92	D	0.613	neutral	None	None	None	None	I
G/Q	0.4408	ambiguous	0.5675	pathogenic	-0.501	Destabilizing	0.739	D	0.603	neutral	None	None	None	None	I
G/R	0.3656	ambiguous	0.4517	ambiguous	-0.113	Destabilizing	0.004	N	0.332	neutral	N	0.488842654	None	None	I
G/S	0.2403	likely_benign	0.341	ambiguous	-0.406	Destabilizing	0.447	N	0.286	neutral	None	None	None	None	I
G/T	0.5357	ambiguous	0.6583	pathogenic	-0.49	Destabilizing	0.617	D	0.537	neutral	None	None	None	None	I
G/V	0.6916	likely_pathogenic	0.7927	pathogenic	-0.384	Destabilizing	0.81	D	0.624	neutral	D	0.548270754	None	None	I
G/W	0.7521	likely_pathogenic	0.8198	pathogenic	-1.062	Destabilizing	0.99	D	0.667	neutral	D	0.548777733	None	None	I
G/Y	0.6797	likely_pathogenic	0.7737	pathogenic	-0.757	Destabilizing	0.972	D	0.623	neutral	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.