TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7850	23773;23774;23775	chr2:178720094;178720093;178720092	chr2:179584821;179584820;179584819
N2AB	7533	22822;22823;22824	chr2:178720094;178720093;178720092	chr2:179584821;179584820;179584819
N2A	6606	20041;20042;20043	chr2:178720094;178720093;178720092	chr2:179584821;179584820;179584819
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-63
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.3169
• 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
I/F	None	None	0.034	D	0.423	0.157	0.151104730317	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
I/V	None	None	None	N	0.105	0.248	0.219573609325	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.1793	likely_benign	0.1642	benign	-2.081	Highly Destabilizing	0.01	N	0.285	neutral	None	None	None	None	I
I/C	0.6722	likely_pathogenic	0.5997	pathogenic	-1.305	Destabilizing	0.452	N	0.539	neutral	None	None	None	None	I
I/D	0.5488	ambiguous	0.5093	ambiguous	-1.836	Destabilizing	0.023	N	0.504	neutral	None	None	None	None	I
I/E	0.3483	ambiguous	0.3196	benign	-1.742	Destabilizing	0.017	N	0.481	neutral	None	None	None	None	I
I/F	0.1507	likely_benign	0.1368	benign	-1.344	Destabilizing	0.034	N	0.423	neutral	D	0.533232902	None	None	I
I/G	0.5802	likely_pathogenic	0.5353	ambiguous	-2.495	Highly Destabilizing	0.046	N	0.471	neutral	None	None	None	None	I
I/H	0.392	ambiguous	0.3618	ambiguous	-1.817	Destabilizing	0.255	N	0.558	neutral	None	None	None	None	I
I/K	0.2818	likely_benign	0.2705	benign	-1.385	Destabilizing	0.001	N	0.489	neutral	None	None	None	None	I
I/L	0.1423	likely_benign	0.1309	benign	-0.959	Destabilizing	None	N	0.22	neutral	N	0.492135641	None	None	I
I/M	0.0988	likely_benign	0.0922	benign	-0.821	Destabilizing	0.035	N	0.457	neutral	D	0.527307008	None	None	I
I/N	0.2089	likely_benign	0.1978	benign	-1.366	Destabilizing	None	N	0.338	neutral	N	0.494231797	None	None	I
I/P	0.947	likely_pathogenic	0.932	pathogenic	-1.307	Destabilizing	0.191	N	0.595	neutral	None	None	None	None	I
I/Q	0.3305	likely_benign	0.3062	benign	-1.442	Destabilizing	0.002	N	0.357	neutral	None	None	None	None	I
I/R	0.2094	likely_benign	0.2032	benign	-0.93	Destabilizing	0.044	N	0.572	neutral	None	None	None	None	I
I/S	0.1897	likely_benign	0.1748	benign	-2.045	Highly Destabilizing	0.001	N	0.245	neutral	N	0.458329712	None	None	I
I/T	0.0793	likely_benign	0.0777	benign	-1.831	Destabilizing	0.005	N	0.425	neutral	N	0.422600985	None	None	I
I/V	0.0636	likely_benign	0.0618	benign	-1.307	Destabilizing	None	N	0.105	neutral	N	0.411866704	None	None	I
I/W	0.7461	likely_pathogenic	0.6992	pathogenic	-1.558	Destabilizing	0.934	D	0.561	neutral	None	None	None	None	I
I/Y	0.4534	ambiguous	0.416	ambiguous	-1.294	Destabilizing	0.037	N	0.601	neutral	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.