TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5442	16549;16550;16551	chr2:178732852;178732851;178732850	chr2:179597579;179597578;179597577
N2AB	5125	15598;15599;15600	chr2:178732852;178732851;178732850	chr2:179597579;179597578;179597577
N2A	4198	12817;12818;12819	chr2:178732852;178732851;178732850	chr2:179597579;179597578;179597577
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-37
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.2576
• Predicted PPI site: N

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	0.046	N	0.313	0.344	0.119812018005	gnomAD-4.0.0	2.05467E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70062E-06	0	0
G/R	None	None	0.203	N	0.613	0.391	0.496364318313	gnomAD-4.0.0	1.59491E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02883E-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	0.0909	likely_benign	0.098	benign	-0.705	Destabilizing	0.046	N	0.313	neutral	N	0.381844867	None	None	N
G/C	0.2579	likely_benign	0.2787	benign	-1.227	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
G/D	0.8765	likely_pathogenic	0.9099	pathogenic	-0.994	Destabilizing	0.986	D	0.728	prob.delet.	None	None	None	None	N
G/E	0.8763	likely_pathogenic	0.906	pathogenic	-1.065	Destabilizing	0.982	D	0.745	deleterious	N	0.490136555	None	None	N
G/F	0.8519	likely_pathogenic	0.8824	pathogenic	-1.215	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
G/H	0.9064	likely_pathogenic	0.922	pathogenic	-1.189	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
G/I	0.596	likely_pathogenic	0.6321	pathogenic	-0.413	Destabilizing	0.986	D	0.828	deleterious	None	None	None	None	N
G/K	0.9532	likely_pathogenic	0.9597	pathogenic	-1.051	Destabilizing	0.973	D	0.747	deleterious	None	None	None	None	N
G/L	0.6877	likely_pathogenic	0.7172	pathogenic	-0.413	Destabilizing	0.973	D	0.8	deleterious	None	None	None	None	N
G/M	0.7535	likely_pathogenic	0.7783	pathogenic	-0.43	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
G/N	0.8092	likely_pathogenic	0.8453	pathogenic	-0.815	Destabilizing	0.986	D	0.622	neutral	None	None	None	None	N
G/P	0.9872	likely_pathogenic	0.99	pathogenic	-0.471	Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
G/Q	0.8686	likely_pathogenic	0.8843	pathogenic	-1.024	Destabilizing	0.986	D	0.758	deleterious	None	None	None	None	N
G/R	0.8645	likely_pathogenic	0.8804	pathogenic	-0.75	Destabilizing	0.203	N	0.613	neutral	N	0.483135116	None	None	N
G/S	0.1219	likely_benign	0.1406	benign	-1.126	Destabilizing	0.386	N	0.379	neutral	None	None	None	None	N
G/T	0.2945	likely_benign	0.3333	benign	-1.106	Destabilizing	0.973	D	0.749	deleterious	None	None	None	None	N
G/V	0.3815	ambiguous	0.4203	ambiguous	-0.471	Destabilizing	0.964	D	0.803	deleterious	N	0.471658795	None	None	N
G/W	0.8701	likely_pathogenic	0.8871	pathogenic	-1.479	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
G/Y	0.8506	likely_pathogenic	0.8784	pathogenic	-1.063	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N

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.