TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5236	15931;15932;15933	chr2:178733683;178733682;178733681	chr2:179598410;179598409;179598408
N2AB	4919	14980;14981;14982	chr2:178733683;178733682;178733681	chr2:179598410;179598409;179598408
N2A	3992	12199;12200;12201	chr2:178733683;178733682;178733681	chr2:179598410;179598409;179598408
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-35
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2511
• 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	rs755295120	-0.068	0.048	D	0.716	0.558	0.365317461125	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	2.02969E-04	None	0	0	None	3.27E-05	None	0	0	0
G/D	rs755295120	-0.068	0.048	D	0.716	0.558	0.365317461125	gnomAD-4.0.0	1.43219E-05	None	None	None	None	I	None	0	1.82924E-04	None	0	0	None	0	0	0	1.43336E-05	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	0.1975	likely_benign	0.395	ambiguous	-0.466	Destabilizing	0.873	D	0.787	deleterious	D	0.709237922	None	None	I
G/C	0.366	ambiguous	0.667	pathogenic	-0.772	Destabilizing	0.998	D	0.789	deleterious	D	0.872828345	None	None	I
G/D	0.1686	likely_benign	0.4796	ambiguous	-0.515	Destabilizing	0.048	N	0.716	prob.delet.	D	0.796337085	None	None	I
G/E	0.312	likely_benign	0.616	pathogenic	-0.583	Destabilizing	0.941	D	0.851	deleterious	None	None	None	None	I
G/F	0.8118	likely_pathogenic	0.955	pathogenic	-0.783	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
G/H	0.6005	likely_pathogenic	0.8933	pathogenic	-0.974	Destabilizing	0.996	D	0.8	deleterious	None	None	None	None	I
G/I	0.7032	likely_pathogenic	0.9222	pathogenic	-0.145	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	I
G/K	0.6521	likely_pathogenic	0.8704	pathogenic	-1.01	Destabilizing	0.97	D	0.854	deleterious	None	None	None	None	I
G/L	0.6954	likely_pathogenic	0.9091	pathogenic	-0.145	Destabilizing	0.97	D	0.819	deleterious	None	None	None	None	I
G/M	0.7431	likely_pathogenic	0.9241	pathogenic	-0.236	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
G/N	0.3465	ambiguous	0.7039	pathogenic	-0.652	Destabilizing	0.941	D	0.863	deleterious	None	None	None	None	I
G/P	0.9576	likely_pathogenic	0.9899	pathogenic	-0.21	Destabilizing	0.985	D	0.847	deleterious	None	None	None	None	I
G/Q	0.433	ambiguous	0.7211	pathogenic	-0.8	Destabilizing	0.97	D	0.837	deleterious	None	None	None	None	I
G/R	0.5072	ambiguous	0.7695	pathogenic	-0.728	Destabilizing	0.96	D	0.84	deleterious	D	0.8727793	None	None	I
G/S	0.1344	likely_benign	0.2667	benign	-0.953	Destabilizing	0.924	D	0.87	deleterious	D	0.822084198	None	None	I
G/T	0.4082	ambiguous	0.6869	pathogenic	-0.926	Destabilizing	0.97	D	0.856	deleterious	None	None	None	None	I
G/V	0.5425	ambiguous	0.8383	pathogenic	-0.21	Destabilizing	0.98	D	0.816	deleterious	D	0.872828345	None	None	I
G/W	0.7002	likely_pathogenic	0.915	pathogenic	-1.119	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	I
G/Y	0.6528	likely_pathogenic	0.9235	pathogenic	-0.689	Destabilizing	0.999	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.