TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22632	68119;68120;68121	chr2:178579136;178579135;178579134	chr2:179443863;179443862;179443861
N2AB	20991	63196;63197;63198	chr2:178579136;178579135;178579134	chr2:179443863;179443862;179443861
N2A	20064	60415;60416;60417	chr2:178579136;178579135;178579134	chr2:179443863;179443862;179443861
N2B	13567	40924;40925;40926	chr2:178579136;178579135;178579134	chr2:179443863;179443862;179443861
Novex-1	13692	41299;41300;41301	chr2:178579136;178579135;178579134	chr2:179443863;179443862;179443861
Novex-2	13759	41500;41501;41502	chr2:178579136;178579135;178579134	chr2:179443863;179443862;179443861
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-127
• Domain position: 73
• Structural Position: 166
• Q(SASA): 0.6424
• 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
K/R	None	None	0.999	N	0.615	0.237	0.346315397577	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.3638	ambiguous	0.3181	benign	-0.018	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
K/C	0.7293	likely_pathogenic	0.7208	pathogenic	-0.302	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
K/D	0.8164	likely_pathogenic	0.7905	pathogenic	0.08	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
K/E	0.2545	likely_benign	0.2211	benign	0.082	Stabilizing	0.999	D	0.674	neutral	N	0.497040029	None	None	I
K/F	0.9127	likely_pathogenic	0.8809	pathogenic	-0.261	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
K/G	0.6164	likely_pathogenic	0.5367	ambiguous	-0.202	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
K/H	0.4886	ambiguous	0.4656	ambiguous	-0.444	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
K/I	0.5196	ambiguous	0.4592	ambiguous	0.384	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
K/L	0.5353	ambiguous	0.4762	ambiguous	0.384	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
K/M	0.3162	likely_benign	0.2836	benign	0.159	Stabilizing	1.0	D	0.616	neutral	N	0.495874227	None	None	I
K/N	0.6941	likely_pathogenic	0.6425	pathogenic	0.165	Stabilizing	1.0	D	0.709	prob.delet.	N	0.515492504	None	None	I
K/P	0.9824	likely_pathogenic	0.973	pathogenic	0.277	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
K/Q	0.1655	likely_benign	0.1493	benign	-0.01	Destabilizing	1.0	D	0.709	prob.delet.	N	0.495943951	None	None	I
K/R	0.0829	likely_benign	0.0828	benign	-0.042	Destabilizing	0.999	D	0.615	neutral	N	0.481918648	None	None	I
K/S	0.5269	ambiguous	0.4732	ambiguous	-0.326	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
K/T	0.2094	likely_benign	0.1857	benign	-0.179	Destabilizing	1.0	D	0.689	prob.neutral	N	0.499696332	None	None	I
K/V	0.3483	ambiguous	0.315	benign	0.277	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
K/W	0.8891	likely_pathogenic	0.8753	pathogenic	-0.277	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
K/Y	0.836	likely_pathogenic	0.7981	pathogenic	0.081	Stabilizing	1.0	D	0.676	prob.neutral	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.