TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7433	22522;22523;22524	chr2:178722490;178722489;178722488	chr2:179587217;179587216;179587215
N2AB	7116	21571;21572;21573	chr2:178722490;178722489;178722488	chr2:179587217;179587216;179587215
N2A	6189	18790;18791;18792	chr2:178722490;178722489;178722488	chr2:179587217;179587216;179587215
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-59
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2898
• 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	rs2078568600	None	1.0	D	0.841	0.665	0.872161657467	gnomAD-4.0.0	1.59222E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8601E-06	0	0
G/V	rs1362341150	-0.336	1.0	D	0.834	0.763	0.950427629675	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.665E-04
G/V	rs1362341150	-0.336	1.0	D	0.834	0.763	0.950427629675	gnomAD-4.0.0	1.36875E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.31411E-05

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	0.5219	ambiguous	0.4631	ambiguous	-0.482	Destabilizing	1.0	D	0.723	prob.delet.	D	0.602234654	None	None	I
G/C	0.7595	likely_pathogenic	0.706	pathogenic	-0.917	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/D	0.4989	ambiguous	0.435	ambiguous	-0.847	Destabilizing	0.966	D	0.571	neutral	None	None	None	None	I
G/E	0.6069	likely_pathogenic	0.5379	ambiguous	-1.001	Destabilizing	1.0	D	0.83	deleterious	D	0.607786964	None	None	I
G/F	0.905	likely_pathogenic	0.8804	pathogenic	-1.1	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/H	0.7776	likely_pathogenic	0.7474	pathogenic	-0.76	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/I	0.9136	likely_pathogenic	0.874	pathogenic	-0.522	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/K	0.8608	likely_pathogenic	0.8243	pathogenic	-1.05	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/L	0.8579	likely_pathogenic	0.8178	pathogenic	-0.522	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/M	0.9083	likely_pathogenic	0.88	pathogenic	-0.448	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/N	0.5379	ambiguous	0.4966	ambiguous	-0.676	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/P	0.9891	likely_pathogenic	0.9826	pathogenic	-0.473	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/Q	0.7268	likely_pathogenic	0.6873	pathogenic	-0.989	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/R	0.7395	likely_pathogenic	0.7018	pathogenic	-0.549	Destabilizing	1.0	D	0.841	deleterious	D	0.602668623	None	None	I
G/S	0.2497	likely_benign	0.239	benign	-0.832	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/T	0.6408	likely_pathogenic	0.5881	pathogenic	-0.922	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/V	0.8434	likely_pathogenic	0.7862	pathogenic	-0.473	Destabilizing	1.0	D	0.834	deleterious	D	0.660447261	None	None	I
G/W	0.848	likely_pathogenic	0.8366	pathogenic	-1.263	Destabilizing	1.0	D	0.819	deleterious	D	0.644629705	None	None	I
G/Y	0.8377	likely_pathogenic	0.7983	pathogenic	-0.928	Destabilizing	1.0	D	0.848	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.