TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4994	15205;15206;15207	chr2:178734944;178734943;178734942	chr2:179599671;179599670;179599669
N2AB	4677	14254;14255;14256	chr2:178734944;178734943;178734942	chr2:179599671;179599670;179599669
N2A	3750	11473;11474;11475	chr2:178734944;178734943;178734942	chr2:179599671;179599670;179599669
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-33
• Domain position: 14
• Structural Position: 18
• Q(SASA): 0.763
• 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/V	None	None	0.037	N	0.311	0.073	0.395745362164	gnomAD-4.0.0	1.60867E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8889E-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
L/A	0.2643	likely_benign	0.304	benign	-0.934	Destabilizing	0.129	N	0.452	neutral	None	None	None	None	I
L/C	0.58	likely_pathogenic	0.6515	pathogenic	-0.725	Destabilizing	0.983	D	0.431	neutral	None	None	None	None	I
L/D	0.7199	likely_pathogenic	0.7825	pathogenic	-0.606	Destabilizing	0.418	N	0.507	neutral	None	None	None	None	I
L/E	0.3361	likely_benign	0.4184	ambiguous	-0.67	Destabilizing	0.264	N	0.512	neutral	None	None	None	None	I
L/F	0.1508	likely_benign	0.1869	benign	-0.743	Destabilizing	0.655	D	0.373	neutral	N	0.513628507	None	None	I
L/G	0.514	ambiguous	0.5746	pathogenic	-1.147	Destabilizing	0.418	N	0.492	neutral	None	None	None	None	I
L/H	0.2008	likely_benign	0.2396	benign	-0.336	Destabilizing	0.921	D	0.495	neutral	N	0.509293798	None	None	I
L/I	0.0971	likely_benign	0.1132	benign	-0.472	Destabilizing	0.002	N	0.263	neutral	N	0.497635111	None	None	I
L/K	0.1478	likely_benign	0.1821	benign	-0.709	Destabilizing	None	N	0.288	neutral	None	None	None	None	I
L/M	0.1144	likely_benign	0.125	benign	-0.496	Destabilizing	0.716	D	0.374	neutral	None	None	None	None	I
L/N	0.3683	ambiguous	0.4251	ambiguous	-0.539	Destabilizing	0.418	N	0.505	neutral	None	None	None	None	I
L/P	0.3343	likely_benign	0.3535	ambiguous	-0.593	Destabilizing	0.794	D	0.5	neutral	N	0.488645922	None	None	I
L/Q	0.1109	likely_benign	0.1372	benign	-0.756	Destabilizing	0.716	D	0.495	neutral	None	None	None	None	I
L/R	0.123	likely_benign	0.1494	benign	-0.079	Destabilizing	0.213	N	0.495	neutral	N	0.458646154	None	None	I
L/S	0.2881	likely_benign	0.335	benign	-0.989	Destabilizing	0.129	N	0.494	neutral	None	None	None	None	I
L/T	0.2161	likely_benign	0.2493	benign	-0.945	Destabilizing	0.01	N	0.252	neutral	None	None	None	None	I
L/V	0.0941	likely_benign	0.1048	benign	-0.593	Destabilizing	0.037	N	0.311	neutral	N	0.489795476	None	None	I
L/W	0.3144	likely_benign	0.3747	ambiguous	-0.777	Destabilizing	0.983	D	0.513	neutral	None	None	None	None	I
L/Y	0.3406	ambiguous	0.4089	ambiguous	-0.553	Destabilizing	0.836	D	0.439	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.