TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21356	64291;64292;64293	chr2:178587145;178587144;178587143	chr2:179451872;179451871;179451870
N2AB	19715	59368;59369;59370	chr2:178587145;178587144;178587143	chr2:179451872;179451871;179451870
N2A	18788	56587;56588;56589	chr2:178587145;178587144;178587143	chr2:179451872;179451871;179451870
N2B	12291	37096;37097;37098	chr2:178587145;178587144;178587143	chr2:179451872;179451871;179451870
Novex-1	12416	37471;37472;37473	chr2:178587145;178587144;178587143	chr2:179451872;179451871;179451870
Novex-2	12483	37672;37673;37674	chr2:178587145;178587144;178587143	chr2:179451872;179451871;179451870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-42
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.7106
• 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
K/N	None	None	0.883	N	0.621	0.116	0.199424873507	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	7.32654E-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
K/A	0.2265	likely_benign	0.2203	benign	-0.074	Destabilizing	0.74	D	0.505	neutral	None	None	None	None	N
K/C	0.514	ambiguous	0.5238	ambiguous	-0.515	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
K/D	0.412	ambiguous	0.3974	ambiguous	-0.406	Destabilizing	0.909	D	0.613	neutral	None	None	None	None	N
K/E	0.1456	likely_benign	0.151	benign	-0.376	Destabilizing	0.682	D	0.497	neutral	N	0.419133819	None	None	N
K/F	0.5927	likely_pathogenic	0.5861	pathogenic	-0.313	Destabilizing	0.996	D	0.697	prob.delet.	None	None	None	None	N
K/G	0.3018	likely_benign	0.2916	benign	-0.244	Destabilizing	0.909	D	0.385	neutral	None	None	None	None	N
K/H	0.2427	likely_benign	0.2442	benign	-0.316	Destabilizing	0.987	D	0.583	neutral	None	None	None	None	N
K/I	0.2639	likely_benign	0.2626	benign	0.306	Stabilizing	0.938	D	0.727	deleterious	N	0.521415611	None	None	N
K/L	0.2502	likely_benign	0.2394	benign	0.306	Stabilizing	0.909	D	0.385	neutral	None	None	None	None	N
K/M	0.198	likely_benign	0.1929	benign	-0.289	Destabilizing	0.996	D	0.581	neutral	None	None	None	None	N
K/N	0.3016	likely_benign	0.2948	benign	-0.133	Destabilizing	0.883	D	0.621	neutral	N	0.449688799	None	None	N
K/P	0.6184	likely_pathogenic	0.571	pathogenic	0.203	Stabilizing	0.984	D	0.605	neutral	None	None	None	None	N
K/Q	0.1119	likely_benign	0.1113	benign	-0.191	Destabilizing	0.883	D	0.633	neutral	N	0.469831998	None	None	N
K/R	0.0873	likely_benign	0.0853	benign	-0.069	Destabilizing	0.007	N	0.312	neutral	N	0.483107939	None	None	N
K/S	0.273	likely_benign	0.2692	benign	-0.428	Destabilizing	0.74	D	0.589	neutral	None	None	None	None	N
K/T	0.1367	likely_benign	0.1338	benign	-0.265	Destabilizing	0.883	D	0.558	neutral	N	0.50915839	None	None	N
K/V	0.209	likely_benign	0.2091	benign	0.203	Stabilizing	0.953	D	0.621	neutral	None	None	None	None	N
K/W	0.6849	likely_pathogenic	0.6809	pathogenic	-0.449	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
K/Y	0.494	ambiguous	0.4882	ambiguous	-0.103	Destabilizing	0.984	D	0.629	neutral	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.