TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26760	80503;80504;80505	chr2:178565854;178565853;178565852	chr2:179430581;179430580;179430579
N2AB	25119	75580;75581;75582	chr2:178565854;178565853;178565852	chr2:179430581;179430580;179430579
N2A	24192	72799;72800;72801	chr2:178565854;178565853;178565852	chr2:179430581;179430580;179430579
N2B	17695	53308;53309;53310	chr2:178565854;178565853;178565852	chr2:179430581;179430580;179430579
Novex-1	17820	53683;53684;53685	chr2:178565854;178565853;178565852	chr2:179430581;179430580;179430579
Novex-2	17887	53884;53885;53886	chr2:178565854;178565853;178565852	chr2:179430581;179430580;179430579
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-82
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.3065
• 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
E/D	rs778292712	-1.34	0.974	D	0.46	0.404	0.20549828249	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.8E-05	None	0	8.89E-06	0
E/D	rs778292712	-1.34	0.974	D	0.46	0.404	0.20549828249	gnomAD-4.0.0	5.47418E-06	None	None	None	None	I	None	5.97872E-05	0	None	0	0	None	0	0	1.79912E-06	3.4781E-05	1.65706E-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
E/A	0.4636	ambiguous	0.4383	ambiguous	-0.801	Destabilizing	0.997	D	0.68	prob.neutral	N	0.473620056	None	None	I
E/C	0.9091	likely_pathogenic	0.9159	pathogenic	-0.696	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
E/D	0.7628	likely_pathogenic	0.7835	pathogenic	-1.525	Destabilizing	0.974	D	0.46	neutral	D	0.530619074	None	None	I
E/F	0.9536	likely_pathogenic	0.9529	pathogenic	-1.039	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
E/G	0.6632	likely_pathogenic	0.6385	pathogenic	-1.135	Destabilizing	1.0	D	0.771	deleterious	N	0.519098184	None	None	I
E/H	0.8993	likely_pathogenic	0.9008	pathogenic	-1.304	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/I	0.5762	likely_pathogenic	0.5755	pathogenic	0.104	Stabilizing	0.999	D	0.887	deleterious	None	None	None	None	I
E/K	0.5197	ambiguous	0.4876	ambiguous	-1.02	Destabilizing	0.998	D	0.544	neutral	N	0.481875716	None	None	I
E/L	0.8269	likely_pathogenic	0.8134	pathogenic	0.104	Stabilizing	0.999	D	0.861	deleterious	None	None	None	None	I
E/M	0.7122	likely_pathogenic	0.6983	pathogenic	0.59	Stabilizing	0.999	D	0.837	deleterious	None	None	None	None	I
E/N	0.8333	likely_pathogenic	0.8364	pathogenic	-1.237	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
E/P	0.9979	likely_pathogenic	0.9977	pathogenic	-0.177	Destabilizing	0.994	D	0.83	deleterious	None	None	None	None	I
E/Q	0.2577	likely_benign	0.2375	benign	-1.072	Destabilizing	0.999	D	0.623	neutral	N	0.484242346	None	None	I
E/R	0.6889	likely_pathogenic	0.6656	pathogenic	-1.011	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/S	0.5584	ambiguous	0.5512	ambiguous	-1.692	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	I
E/T	0.5995	likely_pathogenic	0.6049	pathogenic	-1.394	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	I
E/V	0.3081	likely_benign	0.3096	benign	-0.177	Destabilizing	0.998	D	0.833	deleterious	N	0.462041155	None	None	I
E/W	0.9895	likely_pathogenic	0.9907	pathogenic	-1.219	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
E/Y	0.9471	likely_pathogenic	0.947	pathogenic	-0.881	Destabilizing	1.0	D	0.853	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.