TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33374	100345;100346;100347	chr2:178536989;178536988;178536987	chr2:179401716;179401715;179401714
N2AB	31733	95422;95423;95424	chr2:178536989;178536988;178536987	chr2:179401716;179401715;179401714
N2A	30806	92641;92642;92643	chr2:178536989;178536988;178536987	chr2:179401716;179401715;179401714
N2B	24309	73150;73151;73152	chr2:178536989;178536988;178536987	chr2:179401716;179401715;179401714
Novex-1	24434	73525;73526;73527	chr2:178536989;178536988;178536987	chr2:179401716;179401715;179401714
Novex-2	24501	73726;73727;73728	chr2:178536989;178536988;178536987	chr2:179401716;179401715;179401714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-130
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.4227
• 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
I/V	None	None	0.219	N	0.253	0.108	0.42324137094	gnomAD-4.0.0	1.36885E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79927E-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
I/A	0.5665	likely_pathogenic	0.5347	ambiguous	-1.102	Destabilizing	0.964	D	0.621	neutral	None	None	None	None	I
I/C	0.7688	likely_pathogenic	0.7356	pathogenic	-0.887	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
I/D	0.8389	likely_pathogenic	0.785	pathogenic	-0.269	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
I/E	0.7417	likely_pathogenic	0.7015	pathogenic	-0.33	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
I/F	0.2701	likely_benign	0.2281	benign	-0.986	Destabilizing	0.997	D	0.675	neutral	N	0.516729363	None	None	I
I/G	0.8449	likely_pathogenic	0.8202	pathogenic	-1.318	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
I/H	0.72	likely_pathogenic	0.6552	pathogenic	-0.476	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
I/K	0.5637	ambiguous	0.4995	ambiguous	-0.45	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
I/L	0.1763	likely_benign	0.16	benign	-0.633	Destabilizing	0.817	D	0.28	neutral	N	0.473303873	None	None	I
I/M	0.1658	likely_benign	0.1506	benign	-0.514	Destabilizing	0.997	D	0.705	prob.neutral	N	0.505840365	None	None	I
I/N	0.4007	ambiguous	0.3083	benign	-0.251	Destabilizing	0.999	D	0.803	deleterious	N	0.501413194	None	None	I
I/P	0.8542	likely_pathogenic	0.8332	pathogenic	-0.756	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
I/Q	0.6295	likely_pathogenic	0.5828	pathogenic	-0.516	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	I
I/R	0.5238	ambiguous	0.4491	ambiguous	0.125	Stabilizing	0.999	D	0.807	deleterious	None	None	None	None	I
I/S	0.5006	ambiguous	0.4485	ambiguous	-0.872	Destabilizing	0.997	D	0.753	deleterious	N	0.510552752	None	None	I
I/T	0.3495	ambiguous	0.3276	benign	-0.821	Destabilizing	0.98	D	0.64	neutral	N	0.484694302	None	None	I
I/V	0.0955	likely_benign	0.0959	benign	-0.756	Destabilizing	0.219	N	0.253	neutral	N	0.411159336	None	None	I
I/W	0.9022	likely_pathogenic	0.8756	pathogenic	-0.925	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
I/Y	0.6874	likely_pathogenic	0.6171	pathogenic	-0.672	Destabilizing	0.999	D	0.74	deleterious	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.