TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9180	27763;27764;27765	chr2:178712384;178712383;178712382	chr2:179577111;179577110;179577109
N2AB	8863	26812;26813;26814	chr2:178712384;178712383;178712382	chr2:179577111;179577110;179577109
N2A	7936	24031;24032;24033	chr2:178712384;178712383;178712382	chr2:179577111;179577110;179577109
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-77
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1986
• 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/E	None	None	1.0	D	0.855	0.805	0.820832588438	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02371E-05
G/R	rs1435275543	None	1.0	D	0.861	0.765	0.877214000256	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/R	rs1435275543	None	1.0	D	0.861	0.765	0.877214000256	gnomAD-4.0.0	6.57419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47007E-05	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	0.2582	likely_benign	0.2385	benign	-0.833	Destabilizing	0.999	D	0.805	deleterious	D	0.590488928	None	None	N
G/C	0.7089	likely_pathogenic	0.6468	pathogenic	-0.95	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
G/D	0.7946	likely_pathogenic	0.7458	pathogenic	-1.686	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/E	0.856	likely_pathogenic	0.809	pathogenic	-1.702	Destabilizing	1.0	D	0.855	deleterious	D	0.612351689	None	None	N
G/F	0.9554	likely_pathogenic	0.9359	pathogenic	-1.098	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/H	0.9451	likely_pathogenic	0.9202	pathogenic	-1.633	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/I	0.9418	likely_pathogenic	0.9173	pathogenic	-0.301	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/K	0.9599	likely_pathogenic	0.9357	pathogenic	-1.452	Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
G/L	0.912	likely_pathogenic	0.8726	pathogenic	-0.301	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/M	0.9349	likely_pathogenic	0.91	pathogenic	-0.191	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/N	0.8499	likely_pathogenic	0.811	pathogenic	-1.202	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
G/P	0.9961	likely_pathogenic	0.9935	pathogenic	-0.436	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
G/Q	0.8712	likely_pathogenic	0.8268	pathogenic	-1.334	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/R	0.885	likely_pathogenic	0.8292	pathogenic	-1.162	Destabilizing	1.0	D	0.861	deleterious	D	0.641402631	None	None	N
G/S	0.2515	likely_benign	0.2143	benign	-1.435	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/T	0.7585	likely_pathogenic	0.7	pathogenic	-1.373	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/V	0.8653	likely_pathogenic	0.8201	pathogenic	-0.436	Destabilizing	1.0	D	0.847	deleterious	D	0.657623796	None	None	N
G/W	0.9492	likely_pathogenic	0.9294	pathogenic	-1.585	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
G/Y	0.9461	likely_pathogenic	0.9219	pathogenic	-1.134	Destabilizing	1.0	D	0.848	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.