TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15082	45469;45470;45471	chr2:178621580;178621579;178621578	chr2:179486307;179486306;179486305
N2AB	13441	40546;40547;40548	chr2:178621580;178621579;178621578	chr2:179486307;179486306;179486305
N2A	12514	37765;37766;37767	chr2:178621580;178621579;178621578	chr2:179486307;179486306;179486305
N2B	6017	18274;18275;18276	chr2:178621580;178621579;178621578	chr2:179486307;179486306;179486305
Novex-1	6142	18649;18650;18651	chr2:178621580;178621579;178621578	chr2:179486307;179486306;179486305
Novex-2	6209	18850;18851;18852	chr2:178621580;178621579;178621578	chr2:179486307;179486306;179486305
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-102
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.3741
• 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	rs1400844297	None	1.0	D	0.696	0.475	0.681741161928	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-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	0.2918	likely_benign	0.2464	benign	-0.499	Destabilizing	0.974	D	0.499	neutral	D	0.67915706	None	None	N
G/C	0.5656	likely_pathogenic	0.5094	ambiguous	-0.902	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
G/D	0.2061	likely_benign	0.253	benign	-0.898	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
G/E	0.2684	likely_benign	0.2963	benign	-1.051	Destabilizing	1.0	D	0.696	prob.neutral	D	0.680471531	None	None	N
G/F	0.8396	likely_pathogenic	0.7961	pathogenic	-1.127	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/H	0.6265	likely_pathogenic	0.6141	pathogenic	-0.804	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
G/I	0.6734	likely_pathogenic	0.5674	pathogenic	-0.527	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/K	0.5755	likely_pathogenic	0.5946	pathogenic	-1.098	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/L	0.7255	likely_pathogenic	0.6734	pathogenic	-0.527	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/M	0.7618	likely_pathogenic	0.6988	pathogenic	-0.439	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/N	0.2971	likely_benign	0.2973	benign	-0.684	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
G/P	0.9186	likely_pathogenic	0.8751	pathogenic	-0.482	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
G/Q	0.4919	ambiguous	0.4819	ambiguous	-0.996	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
G/R	0.5325	ambiguous	0.5186	ambiguous	-0.589	Destabilizing	1.0	D	0.739	prob.delet.	D	0.691035666	None	None	N
G/S	0.1793	likely_benign	0.1571	benign	-0.836	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
G/T	0.4378	ambiguous	0.366	ambiguous	-0.925	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
G/V	0.5201	ambiguous	0.4183	ambiguous	-0.482	Destabilizing	1.0	D	0.725	prob.delet.	D	0.742345716	None	None	N
G/W	0.6816	likely_pathogenic	0.6453	pathogenic	-1.297	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
G/Y	0.6611	likely_pathogenic	0.6189	pathogenic	-0.963	Destabilizing	1.0	D	0.763	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.