TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22619	68080;68081;68082	chr2:178579175;178579174;178579173	chr2:179443902;179443901;179443900
N2AB	20978	63157;63158;63159	chr2:178579175;178579174;178579173	chr2:179443902;179443901;179443900
N2A	20051	60376;60377;60378	chr2:178579175;178579174;178579173	chr2:179443902;179443901;179443900
N2B	13554	40885;40886;40887	chr2:178579175;178579174;178579173	chr2:179443902;179443901;179443900
Novex-1	13679	41260;41261;41262	chr2:178579175;178579174;178579173	chr2:179443902;179443901;179443900
Novex-2	13746	41461;41462;41463	chr2:178579175;178579174;178579173	chr2:179443902;179443901;179443900
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-127
• Domain position: 60
• Structural Position: 152
• 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/E	rs886055252	None	0.884	D	0.631	0.559	0.541149246611	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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	0.2217	likely_benign	0.2261	benign	-0.412	Destabilizing	0.996	D	0.753	deleterious	D	0.556360724	None	None	I
G/C	0.4498	ambiguous	0.504	ambiguous	-0.741	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/D	0.5155	ambiguous	0.5723	pathogenic	-0.308	Destabilizing	0.504	D	0.557	neutral	None	None	None	None	I
G/E	0.6067	likely_pathogenic	0.6576	pathogenic	-0.378	Destabilizing	0.884	D	0.631	neutral	D	0.616762818	None	None	I
G/F	0.9211	likely_pathogenic	0.934	pathogenic	-0.792	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/H	0.8301	likely_pathogenic	0.8684	pathogenic	-0.919	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/I	0.8655	likely_pathogenic	0.8949	pathogenic	-0.123	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/K	0.8583	likely_pathogenic	0.8786	pathogenic	-0.85	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
G/L	0.811	likely_pathogenic	0.8303	pathogenic	-0.123	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/M	0.8347	likely_pathogenic	0.8538	pathogenic	-0.229	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/N	0.6241	likely_pathogenic	0.6728	pathogenic	-0.558	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	I
G/P	0.9934	likely_pathogenic	0.9935	pathogenic	-0.178	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/Q	0.6645	likely_pathogenic	0.6996	pathogenic	-0.689	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
G/R	0.7418	likely_pathogenic	0.7636	pathogenic	-0.618	Destabilizing	0.999	D	0.816	deleterious	D	0.616561013	None	None	I
G/S	0.1577	likely_benign	0.1762	benign	-0.864	Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	I
G/T	0.4803	ambiguous	0.539	ambiguous	-0.835	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/V	0.7294	likely_pathogenic	0.7684	pathogenic	-0.178	Destabilizing	0.999	D	0.814	deleterious	D	0.616762818	None	None	I
G/W	0.8753	likely_pathogenic	0.8989	pathogenic	-1.125	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
G/Y	0.8755	likely_pathogenic	0.893	pathogenic	-0.677	Destabilizing	1.0	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.