TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8535	25828;25829;25830	chr2:178717131;178717130;178717129	chr2:179581858;179581857;179581856
N2AB	8218	24877;24878;24879	chr2:178717131;178717130;178717129	chr2:179581858;179581857;179581856
N2A	7291	22096;22097;22098	chr2:178717131;178717130;178717129	chr2:179581858;179581857;179581856
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-70
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2661
• 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/R	None	None	1.0	D	0.853	0.782	0.697169835009	gnomAD-4.0.0	1.59257E-06	None	None	None	None	I	None	0	0	None	0	2.77393E-05	None	0	0	0	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	0.7484	likely_pathogenic	0.7528	pathogenic	-0.336	Destabilizing	0.999	D	0.595	neutral	D	0.601997156	None	None	I
G/C	0.9423	likely_pathogenic	0.9508	pathogenic	-0.855	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/D	0.9313	likely_pathogenic	0.9336	pathogenic	-0.84	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/E	0.9369	likely_pathogenic	0.9448	pathogenic	-1.015	Destabilizing	1.0	D	0.827	deleterious	D	0.560820326	None	None	I
G/F	0.9878	likely_pathogenic	0.9887	pathogenic	-1.117	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/H	0.9736	likely_pathogenic	0.9765	pathogenic	-0.596	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/I	0.9854	likely_pathogenic	0.9868	pathogenic	-0.519	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/K	0.9618	likely_pathogenic	0.9654	pathogenic	-0.93	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/L	0.9779	likely_pathogenic	0.98	pathogenic	-0.519	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/M	0.9841	likely_pathogenic	0.9852	pathogenic	-0.499	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
G/N	0.9494	likely_pathogenic	0.9518	pathogenic	-0.517	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/P	0.9983	likely_pathogenic	0.9987	pathogenic	-0.426	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/Q	0.9338	likely_pathogenic	0.9373	pathogenic	-0.849	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/R	0.897	likely_pathogenic	0.9059	pathogenic	-0.423	Destabilizing	1.0	D	0.853	deleterious	D	0.607306582	None	None	I
G/S	0.6083	likely_pathogenic	0.6025	pathogenic	-0.607	Destabilizing	0.997	D	0.548	neutral	None	None	None	None	I
G/T	0.9277	likely_pathogenic	0.9333	pathogenic	-0.726	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/V	0.9584	likely_pathogenic	0.9621	pathogenic	-0.426	Destabilizing	1.0	D	0.827	deleterious	D	0.656202243	None	None	I
G/W	0.9687	likely_pathogenic	0.9723	pathogenic	-1.254	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/Y	0.979	likely_pathogenic	0.9821	pathogenic	-0.925	Destabilizing	1.0	D	0.848	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.