TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8668	26227;26228;26229	chr2:178715184;178715183;178715182	chr2:179579911;179579910;179579909
N2AB	8351	25276;25277;25278	chr2:178715184;178715183;178715182	chr2:179579911;179579910;179579909
N2A	7424	22495;22496;22497	chr2:178715184;178715183;178715182	chr2:179579911;179579910;179579909
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-72
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3102
• 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/A	None	None	1.0	D	0.775	0.69	0.562354153293	gnomAD-4.0.0	1.59146E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43303E-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	0.7654	likely_pathogenic	0.793	pathogenic	-0.451	Destabilizing	1.0	D	0.775	deleterious	D	0.549767238	None	None	I
G/C	0.9807	likely_pathogenic	0.9832	pathogenic	-0.619	Destabilizing	1.0	D	0.71	prob.delet.	D	0.655330715	None	None	I
G/D	0.9884	likely_pathogenic	0.9852	pathogenic	-0.832	Destabilizing	1.0	D	0.832	deleterious	D	0.638100529	None	None	I
G/E	0.9929	likely_pathogenic	0.9913	pathogenic	-0.81	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/F	0.9972	likely_pathogenic	0.9969	pathogenic	-0.66	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/H	0.9982	likely_pathogenic	0.9981	pathogenic	-0.908	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
G/I	0.9937	likely_pathogenic	0.9928	pathogenic	0.056	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
G/K	0.9982	likely_pathogenic	0.9979	pathogenic	-0.859	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/L	0.9935	likely_pathogenic	0.9944	pathogenic	0.056	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/M	0.9962	likely_pathogenic	0.9965	pathogenic	-0.216	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
G/N	0.9936	likely_pathogenic	0.9931	pathogenic	-0.715	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/P	0.9987	likely_pathogenic	0.9988	pathogenic	-0.073	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/Q	0.997	likely_pathogenic	0.9967	pathogenic	-0.753	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/R	0.996	likely_pathogenic	0.9953	pathogenic	-0.702	Destabilizing	1.0	D	0.813	deleterious	D	0.654927107	None	None	I
G/S	0.8876	likely_pathogenic	0.8923	pathogenic	-0.994	Destabilizing	1.0	D	0.833	deleterious	D	0.563080986	None	None	I
G/T	0.9814	likely_pathogenic	0.9811	pathogenic	-0.867	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/V	0.9823	likely_pathogenic	0.9803	pathogenic	-0.073	Destabilizing	1.0	D	0.787	deleterious	D	0.638907746	None	None	I
G/W	0.9954	likely_pathogenic	0.9948	pathogenic	-1.095	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
G/Y	0.996	likely_pathogenic	0.9955	pathogenic	-0.578	Destabilizing	1.0	D	0.749	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.