TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7391	22396;22397;22398	chr2:178722728;178722727;178722726	chr2:179587455;179587454;179587453
N2AB	7074	21445;21446;21447	chr2:178722728;178722727;178722726	chr2:179587455;179587454;179587453
N2A	6147	18664;18665;18666	chr2:178722728;178722727;178722726	chr2:179587455;179587454;179587453
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-58
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2526
• 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	0.999	D	0.799	0.618	0.611664894473	gnomAD-4.0.0	3.42254E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.64069E-05	1.65821E-05

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	0.2081	likely_benign	0.3293	benign	-0.389	Destabilizing	0.091	N	0.522	neutral	D	0.542895174	None	None	I
G/C	0.5574	ambiguous	0.805	pathogenic	-0.644	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/D	0.5483	ambiguous	0.7745	pathogenic	-0.558	Destabilizing	0.997	D	0.787	deleterious	None	None	None	None	I
G/E	0.6562	likely_pathogenic	0.8609	pathogenic	-0.541	Destabilizing	0.998	D	0.787	deleterious	D	0.647408552	None	None	I
G/F	0.911	likely_pathogenic	0.9722	pathogenic	-0.605	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	I
G/H	0.8468	likely_pathogenic	0.9526	pathogenic	-1.157	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/I	0.8338	likely_pathogenic	0.9536	pathogenic	0.221	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
G/K	0.8375	likely_pathogenic	0.9519	pathogenic	-0.804	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	I
G/L	0.7937	likely_pathogenic	0.932	pathogenic	0.221	Stabilizing	0.999	D	0.798	deleterious	None	None	None	None	I
G/M	0.832	likely_pathogenic	0.9456	pathogenic	0.064	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/N	0.6813	likely_pathogenic	0.8723	pathogenic	-0.652	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	I
G/P	0.9884	likely_pathogenic	0.9965	pathogenic	0.063	Stabilizing	0.998	D	0.799	deleterious	None	None	None	None	I
G/Q	0.6988	likely_pathogenic	0.8763	pathogenic	-0.663	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	I
G/R	0.6674	likely_pathogenic	0.8662	pathogenic	-0.751	Destabilizing	0.999	D	0.799	deleterious	D	0.647206747	None	None	I
G/S	0.1695	likely_benign	0.2888	benign	-1.022	Destabilizing	0.793	D	0.553	neutral	None	None	None	None	I
G/T	0.4961	ambiguous	0.7435	pathogenic	-0.891	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	I
G/V	0.6775	likely_pathogenic	0.8818	pathogenic	0.063	Stabilizing	0.997	D	0.801	deleterious	D	0.647408552	None	None	I
G/W	0.859	likely_pathogenic	0.9533	pathogenic	-1.122	Destabilizing	0.802	D	0.705	prob.neutral	None	None	None	None	I
G/Y	0.8824	likely_pathogenic	0.9679	pathogenic	-0.57	Destabilizing	0.999	D	0.806	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.