TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29961	90106;90107;90108	chr2:178553019;178553018;178553017	chr2:179417746;179417745;179417744
N2AB	28320	85183;85184;85185	chr2:178553019;178553018;178553017	chr2:179417746;179417745;179417744
N2A	27393	82402;82403;82404	chr2:178553019;178553018;178553017	chr2:179417746;179417745;179417744
N2B	20896	62911;62912;62913	chr2:178553019;178553018;178553017	chr2:179417746;179417745;179417744
Novex-1	21021	63286;63287;63288	chr2:178553019;178553018;178553017	chr2:179417746;179417745;179417744
Novex-2	21088	63487;63488;63489	chr2:178553019;178553018;178553017	chr2:179417746;179417745;179417744
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-106
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.3319
• 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/R	None	None	0.996	N	0.863	0.444	0.606262950116	gnomAD-4.0.0	6.85209E-07	None	None	None	None	I	None	0	0	None	0	2.52411E-05	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
G/A	0.9667	likely_pathogenic	0.9539	pathogenic	-0.368	Destabilizing	0.969	D	0.662	neutral	D	0.528795422	None	None	I
G/C	0.9922	likely_pathogenic	0.9881	pathogenic	-0.835	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/D	0.9981	likely_pathogenic	0.9971	pathogenic	-0.653	Destabilizing	0.993	D	0.781	deleterious	None	None	None	None	I
G/E	0.9987	likely_pathogenic	0.9982	pathogenic	-0.814	Destabilizing	0.513	D	0.663	neutral	D	0.551165637	None	None	I
G/F	0.9992	likely_pathogenic	0.9988	pathogenic	-1.098	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/H	0.9992	likely_pathogenic	0.9987	pathogenic	-0.694	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/I	0.9991	likely_pathogenic	0.9986	pathogenic	-0.45	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/K	0.9986	likely_pathogenic	0.9982	pathogenic	-0.848	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	I
G/L	0.9988	likely_pathogenic	0.9983	pathogenic	-0.45	Destabilizing	0.997	D	0.841	deleterious	None	None	None	None	I
G/M	0.9994	likely_pathogenic	0.9991	pathogenic	-0.381	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/N	0.9981	likely_pathogenic	0.9973	pathogenic	-0.46	Destabilizing	0.997	D	0.833	deleterious	None	None	None	None	I
G/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.388	Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	I
G/Q	0.9987	likely_pathogenic	0.998	pathogenic	-0.766	Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	I
G/R	0.9944	likely_pathogenic	0.9922	pathogenic	-0.401	Destabilizing	0.996	D	0.863	deleterious	N	0.521540493	None	None	I
G/S	0.9653	likely_pathogenic	0.9537	pathogenic	-0.617	Destabilizing	0.993	D	0.798	deleterious	None	None	None	None	I
G/T	0.9962	likely_pathogenic	0.9949	pathogenic	-0.708	Destabilizing	0.997	D	0.863	deleterious	None	None	None	None	I
G/V	0.9978	likely_pathogenic	0.9969	pathogenic	-0.388	Destabilizing	0.996	D	0.845	deleterious	D	0.541165685	None	None	I
G/W	0.9983	likely_pathogenic	0.9974	pathogenic	-1.262	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/Y	0.9989	likely_pathogenic	0.9983	pathogenic	-0.903	Destabilizing	1.0	D	0.826	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.