TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35000	105223;105224;105225	chr2:178531617;178531616;178531615	chr2:179396344;179396343;179396342
N2AB	33359	100300;100301;100302	chr2:178531617;178531616;178531615	chr2:179396344;179396343;179396342
N2A	32432	97519;97520;97521	chr2:178531617;178531616;178531615	chr2:179396344;179396343;179396342
N2B	25935	78028;78029;78030	chr2:178531617;178531616;178531615	chr2:179396344;179396343;179396342
Novex-1	26060	78403;78404;78405	chr2:178531617;178531616;178531615	chr2:179396344;179396343;179396342
Novex-2	26127	78604;78605;78606	chr2:178531617;178531616;178531615	chr2:179396344;179396343;179396342
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: Ig-163
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1235
• 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	rs866303280	None	0.826	N	0.534	0.21	0.324986149311	gnomAD-4.0.0	3.1818E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.4108E-04	0	0	3.02334E-05
E/G	None	None	0.959	D	0.546	0.352	0.452264262256	gnomAD-4.0.0	1.5909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
E/A	0.5439	ambiguous	0.6442	pathogenic	-0.971	Destabilizing	0.826	D	0.483	neutral	N	0.462082093	None	None	N
E/C	0.9761	likely_pathogenic	0.987	pathogenic	-0.687	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/D	0.3339	likely_benign	0.5248	ambiguous	-1.467	Destabilizing	0.826	D	0.534	neutral	N	0.477494263	None	None	N
E/F	0.9714	likely_pathogenic	0.9857	pathogenic	-0.731	Destabilizing	0.997	D	0.663	neutral	None	None	None	None	N
E/G	0.7287	likely_pathogenic	0.8315	pathogenic	-1.359	Destabilizing	0.959	D	0.546	neutral	D	0.530019239	None	None	N
E/H	0.8087	likely_pathogenic	0.8969	pathogenic	-1.111	Destabilizing	0.991	D	0.517	neutral	None	None	None	None	N
E/I	0.8202	likely_pathogenic	0.8847	pathogenic	0.102	Stabilizing	0.982	D	0.628	neutral	None	None	None	None	N
E/K	0.6436	likely_pathogenic	0.7627	pathogenic	-1.093	Destabilizing	0.852	D	0.558	neutral	N	0.456425557	None	None	N
E/L	0.8606	likely_pathogenic	0.915	pathogenic	0.102	Stabilizing	0.939	D	0.558	neutral	None	None	None	None	N
E/M	0.8456	likely_pathogenic	0.8895	pathogenic	0.644	Stabilizing	0.999	D	0.616	neutral	None	None	None	None	N
E/N	0.6417	likely_pathogenic	0.7838	pathogenic	-1.392	Destabilizing	0.969	D	0.501	neutral	None	None	None	None	N
E/P	0.997	likely_pathogenic	0.9991	pathogenic	-0.235	Destabilizing	0.997	D	0.537	neutral	None	None	None	None	N
E/Q	0.3358	likely_benign	0.4012	ambiguous	-1.206	Destabilizing	0.31	N	0.441	neutral	N	0.449134226	None	None	N
E/R	0.7226	likely_pathogenic	0.8319	pathogenic	-0.971	Destabilizing	0.939	D	0.495	neutral	None	None	None	None	N
E/S	0.57	likely_pathogenic	0.6868	pathogenic	-1.861	Destabilizing	0.759	D	0.525	neutral	None	None	None	None	N
E/T	0.6295	likely_pathogenic	0.7368	pathogenic	-1.527	Destabilizing	0.079	N	0.353	neutral	None	None	None	None	N
E/V	0.6204	likely_pathogenic	0.7118	pathogenic	-0.235	Destabilizing	0.92	D	0.547	neutral	N	0.457694994	None	None	N
E/W	0.9863	likely_pathogenic	0.9943	pathogenic	-0.703	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
E/Y	0.9355	likely_pathogenic	0.9702	pathogenic	-0.528	Destabilizing	0.997	D	0.613	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.