TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17681	53266;53267;53268	chr2:178607647;178607646;178607645	chr2:179472374;179472373;179472372
N2AB	16040	48343;48344;48345	chr2:178607647;178607646;178607645	chr2:179472374;179472373;179472372
N2A	15113	45562;45563;45564	chr2:178607647;178607646;178607645	chr2:179472374;179472373;179472372
N2B	8616	26071;26072;26073	chr2:178607647;178607646;178607645	chr2:179472374;179472373;179472372
Novex-1	8741	26446;26447;26448	chr2:178607647;178607646;178607645	chr2:179472374;179472373;179472372
Novex-2	8808	26647;26648;26649	chr2:178607647;178607646;178607645	chr2:179472374;179472373;179472372
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-113
• Domain position: 5
• Structural Position: 11
• Q(SASA): 0.3641
• 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	rs2055221235	None	1.0	N	0.764	0.434	0.797513714255	gnomAD-4.0.0	1.36901E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79949E-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
G/A	0.2803	likely_benign	0.2844	benign	-0.416	Destabilizing	0.974	D	0.531	neutral	N	0.486801606	None	None	I
G/C	0.3889	ambiguous	0.3815	ambiguous	-0.906	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
G/D	0.6435	likely_pathogenic	0.7075	pathogenic	-0.679	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
G/E	0.6199	likely_pathogenic	0.6901	pathogenic	-0.809	Destabilizing	1.0	D	0.747	deleterious	N	0.476525897	None	None	I
G/F	0.7807	likely_pathogenic	0.7886	pathogenic	-0.966	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
G/H	0.7046	likely_pathogenic	0.7674	pathogenic	-0.839	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
G/I	0.4856	ambiguous	0.5314	ambiguous	-0.371	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
G/K	0.7914	likely_pathogenic	0.8592	pathogenic	-1.079	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/L	0.7034	likely_pathogenic	0.7287	pathogenic	-0.371	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/M	0.6833	likely_pathogenic	0.7	pathogenic	-0.461	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
G/N	0.5283	ambiguous	0.5487	ambiguous	-0.685	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
G/P	0.9505	likely_pathogenic	0.9593	pathogenic	-0.349	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/Q	0.6355	likely_pathogenic	0.684	pathogenic	-0.923	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/R	0.6617	likely_pathogenic	0.7444	pathogenic	-0.684	Destabilizing	1.0	D	0.764	deleterious	N	0.490631345	None	None	I
G/S	0.2089	likely_benign	0.2179	benign	-0.855	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
G/T	0.3218	likely_benign	0.3501	ambiguous	-0.909	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
G/V	0.3898	ambiguous	0.4322	ambiguous	-0.349	Destabilizing	1.0	D	0.765	deleterious	N	0.459463076	None	None	I
G/W	0.6566	likely_pathogenic	0.7073	pathogenic	-1.195	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
G/Y	0.7014	likely_pathogenic	0.7347	pathogenic	-0.827	Destabilizing	1.0	D	0.752	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.