TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2284	7075;7076;7077	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139
N2AB	2284	7075;7076;7077	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139
N2A	2284	7075;7076;7077	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139
N2B	2238	6937;6938;6939	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139
Novex-1	2238	6937;6938;6939	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139
Novex-2	2238	6937;6938;6939	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139
Novex-3	2284	7075;7076;7077	chr2:178774414;178774413;178774412	chr2:179639141;179639140;179639139

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-12
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1547
• 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/A	rs751111175	-0.492	0.604	N	0.516	0.247	0.06665444	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.76E-05	1.63506E-04
G/A	rs751111175	-0.492	0.604	N	0.516	0.247	0.06665444	gnomAD-4.0.0	3.42106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49682E-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	0.1218	likely_benign	0.1019	benign	-0.474	Destabilizing	0.604	D	0.516	neutral	N	0.30871105	None	None	N
G/C	0.5698	likely_pathogenic	0.4781	ambiguous	-0.932	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
G/D	0.9876	likely_pathogenic	0.9822	pathogenic	-0.671	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
G/E	0.9822	likely_pathogenic	0.9729	pathogenic	-0.663	Destabilizing	0.999	D	0.869	deleterious	N	0.44739744	None	None	N
G/F	0.9686	likely_pathogenic	0.9523	pathogenic	-0.658	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
G/H	0.9903	likely_pathogenic	0.9843	pathogenic	-1.195	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/I	0.7861	likely_pathogenic	0.703	pathogenic	0.119	Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/K	0.9903	likely_pathogenic	0.986	pathogenic	-1.031	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
G/L	0.8689	likely_pathogenic	0.8127	pathogenic	0.119	Stabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
G/M	0.911	likely_pathogenic	0.8623	pathogenic	-0.111	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/N	0.9784	likely_pathogenic	0.9688	pathogenic	-0.864	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
G/P	0.996	likely_pathogenic	0.9948	pathogenic	-0.033	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
G/Q	0.9791	likely_pathogenic	0.9682	pathogenic	-0.885	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
G/R	0.9736	likely_pathogenic	0.961	pathogenic	-0.925	Destabilizing	0.999	D	0.888	deleterious	N	0.44739744	None	None	N
G/S	0.378	ambiguous	0.3113	benign	-1.231	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
G/T	0.5973	likely_pathogenic	0.5056	ambiguous	-1.104	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
G/V	0.5924	likely_pathogenic	0.4866	ambiguous	-0.033	Destabilizing	0.997	D	0.866	deleterious	N	0.38813058	None	None	N
G/W	0.982	likely_pathogenic	0.9706	pathogenic	-1.123	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
G/Y	0.9802	likely_pathogenic	0.9669	pathogenic	-0.611	Destabilizing	1.0	D	0.887	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.