TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7497	22714;22715;22716	chr2:178722298;178722297;178722296	chr2:179587025;179587024;179587023
N2AB	7180	21763;21764;21765	chr2:178722298;178722297;178722296	chr2:179587025;179587024;179587023
N2A	6253	18982;18983;18984	chr2:178722298;178722297;178722296	chr2:179587025;179587024;179587023
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-59
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.6943
• 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
L/F	None	None	0.933	N	0.404	0.233	0.416075642716	gnomAD-4.0.0	1.60301E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.45319E-05	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
L/A	0.162	likely_benign	0.1801	benign	-0.442	Destabilizing	0.024	N	0.309	neutral	None	None	None	None	I
L/C	0.5171	ambiguous	0.5437	ambiguous	-0.744	Destabilizing	0.997	D	0.528	neutral	None	None	None	None	I
L/D	0.6344	likely_pathogenic	0.6335	pathogenic	-0.313	Destabilizing	0.99	D	0.58	neutral	None	None	None	None	I
L/E	0.352	ambiguous	0.3462	ambiguous	-0.412	Destabilizing	0.952	D	0.544	neutral	None	None	None	None	I
L/F	0.1115	likely_benign	0.1177	benign	-0.658	Destabilizing	0.933	D	0.404	neutral	N	0.496194667	None	None	I
L/G	0.4713	ambiguous	0.5013	ambiguous	-0.53	Destabilizing	0.93	D	0.566	neutral	None	None	None	None	I
L/H	0.2025	likely_benign	0.2125	benign	0.106	Stabilizing	0.997	D	0.579	neutral	N	0.49829361	None	None	I
L/I	0.0794	likely_benign	0.0861	benign	-0.333	Destabilizing	0.057	N	0.345	neutral	N	0.458388427	None	None	I
L/K	0.281	likely_benign	0.2894	benign	-0.32	Destabilizing	0.442	N	0.557	neutral	None	None	None	None	I
L/M	0.1164	likely_benign	0.1239	benign	-0.588	Destabilizing	0.918	D	0.425	neutral	None	None	None	None	I
L/N	0.3731	ambiguous	0.3899	ambiguous	-0.166	Destabilizing	0.997	D	0.582	neutral	None	None	None	None	I
L/P	0.6787	likely_pathogenic	0.7018	pathogenic	-0.343	Destabilizing	0.986	D	0.569	neutral	N	0.510548669	None	None	I
L/Q	0.1434	likely_benign	0.1543	benign	-0.363	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	I
L/R	0.1708	likely_benign	0.1841	benign	0.163	Stabilizing	0.966	D	0.591	neutral	N	0.489468673	None	None	I
L/S	0.2048	likely_benign	0.2251	benign	-0.529	Destabilizing	0.869	D	0.559	neutral	None	None	None	None	I
L/T	0.208	likely_benign	0.2278	benign	-0.531	Destabilizing	0.799	D	0.47	neutral	None	None	None	None	I
L/V	0.0784	likely_benign	0.0873	benign	-0.343	Destabilizing	None	N	0.202	neutral	N	0.426390652	None	None	I
L/W	0.2107	likely_benign	0.22	benign	-0.674	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	I
L/Y	0.2981	likely_benign	0.3019	benign	-0.437	Destabilizing	0.815	D	0.521	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.