TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25612	77059;77060;77061	chr2:178569298;178569297;178569296	chr2:179434025;179434024;179434023
N2AB	23971	72136;72137;72138	chr2:178569298;178569297;178569296	chr2:179434025;179434024;179434023
N2A	23044	69355;69356;69357	chr2:178569298;178569297;178569296	chr2:179434025;179434024;179434023
N2B	16547	49864;49865;49866	chr2:178569298;178569297;178569296	chr2:179434025;179434024;179434023
Novex-1	16672	50239;50240;50241	chr2:178569298;178569297;178569296	chr2:179434025;179434024;179434023
Novex-2	16739	50440;50441;50442	chr2:178569298;178569297;178569296	chr2:179434025;179434024;179434023
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: Fn3-74
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.2707
• Predicted PPI site: N

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	rs1707240113	None	None	N	0.133	0.118	0.115124310173	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
E/A	0.1273	likely_benign	0.1513	benign	-0.677	Destabilizing	0.118	N	0.565	neutral	N	0.486688336	None	None	N
E/C	0.7612	likely_pathogenic	0.8287	pathogenic	-0.137	Destabilizing	0.936	D	0.674	neutral	None	None	None	None	N
E/D	0.0756	likely_benign	0.0825	benign	-0.548	Destabilizing	None	N	0.133	neutral	N	0.45387275	None	None	N
E/F	0.7352	likely_pathogenic	0.8144	pathogenic	-0.436	Destabilizing	0.964	D	0.687	prob.neutral	None	None	None	None	N
E/G	0.142	likely_benign	0.1631	benign	-0.927	Destabilizing	0.309	N	0.567	neutral	N	0.485802963	None	None	N
E/H	0.3581	ambiguous	0.4378	ambiguous	-0.435	Destabilizing	0.863	D	0.609	neutral	None	None	None	None	N
E/I	0.44	ambiguous	0.5331	ambiguous	-0.032	Destabilizing	0.523	D	0.729	prob.delet.	None	None	None	None	N
E/K	0.1877	likely_benign	0.2188	benign	0.111	Stabilizing	0.199	N	0.491	neutral	N	0.485994001	None	None	N
E/L	0.4432	ambiguous	0.5316	ambiguous	-0.032	Destabilizing	0.523	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.465	ambiguous	0.5427	ambiguous	0.255	Stabilizing	0.693	D	0.623	neutral	None	None	None	None	N
E/N	0.1327	likely_benign	0.1621	benign	-0.312	Destabilizing	0.112	N	0.601	neutral	None	None	None	None	N
E/P	0.9248	likely_pathogenic	0.9394	pathogenic	-0.227	Destabilizing	0.14	N	0.706	prob.neutral	None	None	None	None	N
E/Q	0.138	likely_benign	0.1562	benign	-0.255	Destabilizing	0.384	N	0.587	neutral	N	0.48319607	None	None	N
E/R	0.3077	likely_benign	0.3674	ambiguous	0.287	Stabilizing	0.536	D	0.651	neutral	None	None	None	None	N
E/S	0.1316	likely_benign	0.161	benign	-0.496	Destabilizing	0.082	N	0.497	neutral	None	None	None	None	N
E/T	0.1852	likely_benign	0.2269	benign	-0.287	Destabilizing	0.463	N	0.633	neutral	None	None	None	None	N
E/V	0.2811	likely_benign	0.3396	benign	-0.227	Destabilizing	0.37	N	0.667	neutral	N	0.498996147	None	None	N
E/W	0.8898	likely_pathogenic	0.9295	pathogenic	-0.211	Destabilizing	0.986	D	0.675	prob.neutral	None	None	None	None	N
E/Y	0.5708	likely_pathogenic	0.678	pathogenic	-0.178	Destabilizing	0.986	D	0.654	neutral	None	None	None	None	N

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.