TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8712	26359;26360;26361	chr2:178715052;178715051;178715050	chr2:179579779;179579778;179579777
N2AB	8395	25408;25409;25410	chr2:178715052;178715051;178715050	chr2:179579779;179579778;179579777
N2A	7468	22627;22628;22629	chr2:178715052;178715051;178715050	chr2:179579779;179579778;179579777
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-72
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3986
• 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	0.534	N	0.57	0.218	0.271763555656	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.1246	likely_benign	0.1562	benign	-0.593	Destabilizing	0.382	N	0.636	neutral	N	0.485972726	None	None	N
E/C	0.7363	likely_pathogenic	0.8155	pathogenic	-0.171	Destabilizing	0.993	D	0.728	prob.delet.	None	None	None	None	N
E/D	0.0894	likely_benign	0.0934	benign	-0.409	Destabilizing	None	N	0.323	neutral	N	0.485575028	None	None	N
E/F	0.5305	ambiguous	0.6223	pathogenic	-0.201	Destabilizing	0.985	D	0.729	prob.delet.	None	None	None	None	N
E/G	0.1552	likely_benign	0.2052	benign	-0.832	Destabilizing	0.804	D	0.627	neutral	N	0.509218769	None	None	N
E/H	0.3177	likely_benign	0.409	ambiguous	-0.025	Destabilizing	0.939	D	0.626	neutral	None	None	None	None	N
E/I	0.1902	likely_benign	0.2318	benign	0.023	Stabilizing	0.91	D	0.734	prob.delet.	None	None	None	None	N
E/K	0.1036	likely_benign	0.1521	benign	0.317	Stabilizing	0.534	D	0.57	neutral	N	0.494538441	None	None	N
E/L	0.2421	likely_benign	0.3097	benign	0.023	Stabilizing	0.833	D	0.686	prob.neutral	None	None	None	None	N
E/M	0.2916	likely_benign	0.3597	ambiguous	0.176	Stabilizing	0.954	D	0.731	prob.delet.	None	None	None	None	N
E/N	0.1489	likely_benign	0.1841	benign	-0.249	Destabilizing	0.248	N	0.557	neutral	None	None	None	None	N
E/P	0.4885	ambiguous	0.5657	pathogenic	-0.163	Destabilizing	0.6	D	0.708	prob.delet.	None	None	None	None	N
E/Q	0.1083	likely_benign	0.1332	benign	-0.168	Destabilizing	0.129	N	0.299	neutral	N	0.502024561	None	None	N
E/R	0.1934	likely_benign	0.2841	benign	0.546	Stabilizing	0.914	D	0.607	neutral	None	None	None	None	N
E/S	0.1454	likely_benign	0.179	benign	-0.392	Destabilizing	0.06	N	0.318	neutral	None	None	None	None	N
E/T	0.1499	likely_benign	0.1795	benign	-0.177	Destabilizing	0.531	D	0.633	neutral	None	None	None	None	N
E/V	0.1286	likely_benign	0.1529	benign	-0.163	Destabilizing	0.844	D	0.699	prob.neutral	N	0.481804005	None	None	N
E/W	0.7486	likely_pathogenic	0.8288	pathogenic	0.073	Stabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
E/Y	0.3935	ambiguous	0.4894	ambiguous	0.078	Stabilizing	0.994	D	0.739	prob.delet.	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.