TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30493	91702;91703;91704	chr2:178551054;178551053;178551052	chr2:179415781;179415780;179415779
N2AB	28852	86779;86780;86781	chr2:178551054;178551053;178551052	chr2:179415781;179415780;179415779
N2A	27925	83998;83999;84000	chr2:178551054;178551053;178551052	chr2:179415781;179415780;179415779
N2B	21428	64507;64508;64509	chr2:178551054;178551053;178551052	chr2:179415781;179415780;179415779
Novex-1	21553	64882;64883;64884	chr2:178551054;178551053;178551052	chr2:179415781;179415780;179415779
Novex-2	21620	65083;65084;65085	chr2:178551054;178551053;178551052	chr2:179415781;179415780;179415779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-110
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1264
• 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/K	None	None	0.999	N	0.611	0.39	0.339316883193	gnomAD-4.0.0	4.7771E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57927E-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	0.6037	likely_pathogenic	0.672	pathogenic	-1.254	Destabilizing	0.999	D	0.719	prob.delet.	N	0.472257838	None	None	N
E/C	0.9571	likely_pathogenic	0.9666	pathogenic	-0.416	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/D	0.6429	likely_pathogenic	0.6654	pathogenic	-1.361	Destabilizing	0.999	D	0.607	neutral	N	0.478120415	None	None	N
E/F	0.9775	likely_pathogenic	0.9842	pathogenic	-0.809	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/G	0.8156	likely_pathogenic	0.8574	pathogenic	-1.688	Destabilizing	1.0	D	0.745	deleterious	N	0.499769842	None	None	N
E/H	0.9103	likely_pathogenic	0.9324	pathogenic	-0.736	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
E/I	0.8506	likely_pathogenic	0.8913	pathogenic	-0.01	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/K	0.8403	likely_pathogenic	0.8837	pathogenic	-0.816	Destabilizing	0.999	D	0.611	neutral	N	0.498818393	None	None	N
E/L	0.9145	likely_pathogenic	0.9417	pathogenic	-0.01	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.8765	likely_pathogenic	0.9125	pathogenic	0.709	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/N	0.8569	likely_pathogenic	0.8851	pathogenic	-1.206	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/P	0.9971	likely_pathogenic	0.9982	pathogenic	-0.408	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/Q	0.381	ambiguous	0.4249	ambiguous	-0.926	Destabilizing	1.0	D	0.687	prob.neutral	N	0.444311904	None	None	N
E/R	0.8617	likely_pathogenic	0.8961	pathogenic	-0.72	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/S	0.6788	likely_pathogenic	0.7269	pathogenic	-1.872	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/T	0.8048	likely_pathogenic	0.8535	pathogenic	-1.447	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/V	0.7291	likely_pathogenic	0.7928	pathogenic	-0.408	Destabilizing	1.0	D	0.749	deleterious	N	0.474749454	None	None	N
E/W	0.9937	likely_pathogenic	0.9955	pathogenic	-0.73	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/Y	0.959	likely_pathogenic	0.9704	pathogenic	-0.514	Destabilizing	1.0	D	0.804	deleterious	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.