TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25439	76540;76541;76542	chr2:178569817;178569816;178569815	chr2:179434544;179434543;179434542
N2AB	23798	71617;71618;71619	chr2:178569817;178569816;178569815	chr2:179434544;179434543;179434542
N2A	22871	68836;68837;68838	chr2:178569817;178569816;178569815	chr2:179434544;179434543;179434542
N2B	16374	49345;49346;49347	chr2:178569817;178569816;178569815	chr2:179434544;179434543;179434542
Novex-1	16499	49720;49721;49722	chr2:178569817;178569816;178569815	chr2:179434544;179434543;179434542
Novex-2	16566	49921;49922;49923	chr2:178569817;178569816;178569815	chr2:179434544;179434543;179434542
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: Fn3-73
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.101
• 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/R	None	None	0.999	N	0.882	0.386	0.517819333224	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85923E-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	0.3385	likely_benign	0.2621	benign	-0.612	Destabilizing	0.619	D	0.385	neutral	N	0.515318279	None	None	N
G/C	0.5877	likely_pathogenic	0.5353	ambiguous	-0.939	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/D	0.8874	likely_pathogenic	0.879	pathogenic	-1.224	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
G/E	0.8992	likely_pathogenic	0.8987	pathogenic	-1.174	Destabilizing	0.998	D	0.857	deleterious	N	0.472104983	None	None	N
G/F	0.9547	likely_pathogenic	0.9435	pathogenic	-0.674	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/H	0.8758	likely_pathogenic	0.8627	pathogenic	-1.355	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/I	0.9518	likely_pathogenic	0.9384	pathogenic	0.084	Stabilizing	0.999	D	0.894	deleterious	None	None	None	None	N
G/K	0.924	likely_pathogenic	0.9357	pathogenic	-0.893	Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	N
G/L	0.9337	likely_pathogenic	0.9167	pathogenic	0.084	Stabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
G/M	0.928	likely_pathogenic	0.9133	pathogenic	-0.18	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/N	0.7718	likely_pathogenic	0.7752	pathogenic	-0.814	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
G/P	0.9989	likely_pathogenic	0.9984	pathogenic	-0.105	Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
G/Q	0.8508	likely_pathogenic	0.8573	pathogenic	-0.838	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
G/R	0.8489	likely_pathogenic	0.8638	pathogenic	-0.869	Destabilizing	0.999	D	0.882	deleterious	N	0.475245309	None	None	N
G/S	0.242	likely_benign	0.2162	benign	-1.177	Destabilizing	0.935	D	0.388	neutral	None	None	None	None	N
G/T	0.6957	likely_pathogenic	0.6838	pathogenic	-1.028	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
G/V	0.8901	likely_pathogenic	0.8669	pathogenic	-0.105	Destabilizing	0.998	D	0.863	deleterious	N	0.500630945	None	None	N
G/W	0.9234	likely_pathogenic	0.9044	pathogenic	-1.201	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
G/Y	0.8711	likely_pathogenic	0.8549	pathogenic	-0.675	Destabilizing	1.0	D	0.887	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.