TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7216	21871;21872;21873	chr2:178723454;178723453;178723452	chr2:179588181;179588180;179588179
N2AB	6899	20920;20921;20922	chr2:178723454;178723453;178723452	chr2:179588181;179588180;179588179
N2A	5972	18139;18140;18141	chr2:178723454;178723453;178723452	chr2:179588181;179588180;179588179
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-56
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2442
• 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/D	rs766206440	-0.554	1.0	D	0.841	0.622	0.601523639021	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
G/D	rs766206440	-0.554	1.0	D	0.841	0.622	0.601523639021	gnomAD-4.0.0	1.5931E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02847E-05
G/S	None	None	1.0	D	0.79	0.638	0.545611132464	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5754	likely_pathogenic	0.523	ambiguous	-0.355	Destabilizing	1.0	D	0.734	prob.delet.	D	0.621731151	None	None	I
G/C	0.8153	likely_pathogenic	0.7831	pathogenic	-0.836	Destabilizing	1.0	D	0.799	deleterious	D	0.616209202	None	None	I
G/D	0.7734	likely_pathogenic	0.7384	pathogenic	-0.922	Destabilizing	1.0	D	0.841	deleterious	D	0.605308182	None	None	I
G/E	0.8002	likely_pathogenic	0.7648	pathogenic	-1.105	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/F	0.9423	likely_pathogenic	0.9233	pathogenic	-1.214	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/H	0.8971	likely_pathogenic	0.873	pathogenic	-0.584	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/I	0.9305	likely_pathogenic	0.9071	pathogenic	-0.576	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/K	0.8742	likely_pathogenic	0.8462	pathogenic	-0.834	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/L	0.9094	likely_pathogenic	0.8831	pathogenic	-0.576	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/M	0.9392	likely_pathogenic	0.9222	pathogenic	-0.461	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/N	0.8267	likely_pathogenic	0.8041	pathogenic	-0.461	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/P	0.9945	likely_pathogenic	0.9923	pathogenic	-0.472	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/Q	0.8097	likely_pathogenic	0.7717	pathogenic	-0.825	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/R	0.7282	likely_pathogenic	0.686	pathogenic	-0.311	Destabilizing	1.0	D	0.853	deleterious	D	0.605913594	None	None	I
G/S	0.3807	ambiguous	0.3543	ambiguous	-0.532	Destabilizing	1.0	D	0.79	deleterious	D	0.609285341	None	None	I
G/T	0.8059	likely_pathogenic	0.7656	pathogenic	-0.663	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/V	0.8655	likely_pathogenic	0.825	pathogenic	-0.472	Destabilizing	1.0	D	0.821	deleterious	D	0.64807648	None	None	I
G/W	0.9067	likely_pathogenic	0.8762	pathogenic	-1.326	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/Y	0.9137	likely_pathogenic	0.8922	pathogenic	-0.995	Destabilizing	1.0	D	0.827	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.