TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5382	16369;16370;16371	chr2:178733032;178733031;178733030	chr2:179597759;179597758;179597757
N2AB	5065	15418;15419;15420	chr2:178733032;178733031;178733030	chr2:179597759;179597758;179597757
N2A	4138	12637;12638;12639	chr2:178733032;178733031;178733030	chr2:179597759;179597758;179597757
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-37
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3224
• 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	None	None	1.0	D	0.833	0.574	0.647653543843	gnomAD-4.0.0	6.84355E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99549E-07	0	0
G/V	None	None	1.0	D	0.781	0.602	0.784472299234	gnomAD-4.0.0	6.84355E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99549E-07	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	0.8287	likely_pathogenic	0.8201	pathogenic	-0.28	Destabilizing	1.0	D	0.781	deleterious	D	0.559518153	None	None	I
G/C	0.9836	likely_pathogenic	0.9827	pathogenic	-0.633	Destabilizing	1.0	D	0.705	prob.neutral	D	0.629560439	None	None	I
G/D	0.9955	likely_pathogenic	0.9951	pathogenic	-0.471	Destabilizing	1.0	D	0.833	deleterious	D	0.653887725	None	None	I
G/E	0.9969	likely_pathogenic	0.9968	pathogenic	-0.586	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/F	0.9975	likely_pathogenic	0.9973	pathogenic	-0.836	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
G/H	0.9986	likely_pathogenic	0.9986	pathogenic	-0.652	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
G/I	0.9952	likely_pathogenic	0.9951	pathogenic	-0.214	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
G/K	0.9986	likely_pathogenic	0.9984	pathogenic	-0.812	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/L	0.9956	likely_pathogenic	0.9955	pathogenic	-0.214	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/M	0.9979	likely_pathogenic	0.9981	pathogenic	-0.372	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
G/N	0.9964	likely_pathogenic	0.9964	pathogenic	-0.39	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/P	0.9984	likely_pathogenic	0.9984	pathogenic	-0.199	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
G/Q	0.9971	likely_pathogenic	0.9972	pathogenic	-0.602	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/R	0.9941	likely_pathogenic	0.993	pathogenic	-0.459	Destabilizing	1.0	D	0.802	deleterious	D	0.638443416	None	None	I
G/S	0.8567	likely_pathogenic	0.8754	pathogenic	-0.57	Destabilizing	1.0	D	0.833	deleterious	D	0.570045925	None	None	I
G/T	0.9801	likely_pathogenic	0.984	pathogenic	-0.607	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/V	0.9851	likely_pathogenic	0.9848	pathogenic	-0.199	Destabilizing	1.0	D	0.781	deleterious	D	0.62915683	None	None	I
G/W	0.9965	likely_pathogenic	0.9962	pathogenic	-1.092	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
G/Y	0.9976	likely_pathogenic	0.9974	pathogenic	-0.691	Destabilizing	1.0	D	0.739	prob.delet.	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.