TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19159	57700;57701;57702	chr2:178597607;178597606;178597605	chr2:179462334;179462333;179462332
N2AB	17518	52777;52778;52779	chr2:178597607;178597606;178597605	chr2:179462334;179462333;179462332
N2A	16591	49996;49997;49998	chr2:178597607;178597606;178597605	chr2:179462334;179462333;179462332
N2B	10094	30505;30506;30507	chr2:178597607;178597606;178597605	chr2:179462334;179462333;179462332
Novex-1	10219	30880;30881;30882	chr2:178597607;178597606;178597605	chr2:179462334;179462333;179462332
Novex-2	10286	31081;31082;31083	chr2:178597607;178597606;178597605	chr2:179462334;179462333;179462332
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-117
• Domain position: 65
• Structural Position: 152
• Q(SASA): 0.213
• 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/D	None	None	1.0	D	0.847	0.618	0.693435513012	gnomAD-4.0.0	2.05342E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69898E-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	0.814	likely_pathogenic	0.8579	pathogenic	-0.797	Destabilizing	1.0	D	0.743	deleterious	D	0.577952037	None	None	I
G/C	0.9775	likely_pathogenic	0.9834	pathogenic	-0.936	Destabilizing	1.0	D	0.793	deleterious	D	0.626049404	None	None	I
G/D	0.9813	likely_pathogenic	0.9854	pathogenic	-1.849	Destabilizing	1.0	D	0.847	deleterious	D	0.609626434	None	None	I
G/E	0.9937	likely_pathogenic	0.9948	pathogenic	-1.818	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/F	0.9969	likely_pathogenic	0.9974	pathogenic	-0.945	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/H	0.9975	likely_pathogenic	0.9981	pathogenic	-1.708	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
G/I	0.9972	likely_pathogenic	0.9978	pathogenic	-0.115	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
G/K	0.9966	likely_pathogenic	0.9972	pathogenic	-1.345	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
G/L	0.9947	likely_pathogenic	0.9956	pathogenic	-0.115	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/M	0.9958	likely_pathogenic	0.9967	pathogenic	-0.074	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/N	0.9881	likely_pathogenic	0.9896	pathogenic	-1.211	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/P	0.9997	likely_pathogenic	0.9997	pathogenic	-0.299	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
G/Q	0.9939	likely_pathogenic	0.9951	pathogenic	-1.268	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/R	0.9918	likely_pathogenic	0.9936	pathogenic	-1.177	Destabilizing	1.0	D	0.844	deleterious	D	0.625847599	None	None	I
G/S	0.88	likely_pathogenic	0.9121	pathogenic	-1.474	Destabilizing	1.0	D	0.847	deleterious	D	0.599905879	None	None	I
G/T	0.9853	likely_pathogenic	0.9885	pathogenic	-1.36	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/V	0.9916	likely_pathogenic	0.9935	pathogenic	-0.299	Destabilizing	1.0	D	0.829	deleterious	D	0.610030043	None	None	I
G/W	0.9967	likely_pathogenic	0.9977	pathogenic	-1.546	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/Y	0.996	likely_pathogenic	0.9968	pathogenic	-1.049	Destabilizing	1.0	D	0.812	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.