TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27324	82195;82196;82197	chr2:178564162;178564161;178564160	chr2:179428889;179428888;179428887
N2AB	25683	77272;77273;77274	chr2:178564162;178564161;178564160	chr2:179428889;179428888;179428887
N2A	24756	74491;74492;74493	chr2:178564162;178564161;178564160	chr2:179428889;179428888;179428887
N2B	18259	55000;55001;55002	chr2:178564162;178564161;178564160	chr2:179428889;179428888;179428887
Novex-1	18384	55375;55376;55377	chr2:178564162;178564161;178564160	chr2:179428889;179428888;179428887
Novex-2	18451	55576;55577;55578	chr2:178564162;178564161;178564160	chr2:179428889;179428888;179428887
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-140
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.4209
• 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
E/G	None	None	1.0	N	0.761	0.468	0.539612970712	gnomAD-4.0.0	6.84216E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-07	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
E/A	0.2262	likely_benign	0.2394	benign	-0.638	Destabilizing	0.999	D	0.692	prob.neutral	N	0.49435329	None	None	N
E/C	0.8843	likely_pathogenic	0.8992	pathogenic	-0.324	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.1573	likely_benign	0.1912	benign	-0.692	Destabilizing	0.999	D	0.456	neutral	N	0.50435279	None	None	N
E/F	0.791	likely_pathogenic	0.8147	pathogenic	-0.083	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/G	0.3039	likely_benign	0.3277	benign	-0.948	Destabilizing	1.0	D	0.761	deleterious	N	0.498342989	None	None	N
E/H	0.5641	likely_pathogenic	0.5986	pathogenic	-0.102	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/I	0.3538	ambiguous	0.3633	ambiguous	0.189	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/K	0.3077	likely_benign	0.3427	ambiguous	-0.074	Destabilizing	0.999	D	0.586	neutral	N	0.508294386	None	None	N
E/L	0.5123	ambiguous	0.5195	ambiguous	0.189	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/M	0.4906	ambiguous	0.5044	ambiguous	0.376	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.3076	likely_benign	0.3421	ambiguous	-0.638	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/P	0.9784	likely_pathogenic	0.9865	pathogenic	-0.065	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/Q	0.1944	likely_benign	0.2008	benign	-0.53	Destabilizing	1.0	D	0.615	neutral	N	0.512470841	None	None	N
E/R	0.4807	ambiguous	0.5246	ambiguous	0.227	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/S	0.2801	likely_benign	0.2918	benign	-0.849	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/T	0.2494	likely_benign	0.2555	benign	-0.586	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/V	0.2112	likely_benign	0.2129	benign	-0.065	Destabilizing	1.0	D	0.82	deleterious	D	0.525093422	None	None	N
E/W	0.9334	likely_pathogenic	0.9448	pathogenic	0.203	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Y	0.7054	likely_pathogenic	0.7394	pathogenic	0.189	Stabilizing	1.0	D	0.801	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.