TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13688	41287;41288;41289	chr2:178636665;178636664;178636663	chr2:179501392;179501391;179501390
N2AB	12047	36364;36365;36366	chr2:178636665;178636664;178636663	chr2:179501392;179501391;179501390
N2A	11120	33583;33584;33585	chr2:178636665;178636664;178636663	chr2:179501392;179501391;179501390
N2B	4623	14092;14093;14094	chr2:178636665;178636664;178636663	chr2:179501392;179501391;179501390
Novex-1	4748	14467;14468;14469	chr2:178636665;178636664;178636663	chr2:179501392;179501391;179501390
Novex-2	4815	14668;14669;14670	chr2:178636665;178636664;178636663	chr2:179501392;179501391;179501390
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-87
• Domain position: 5
• Structural Position: 7
• Q(SASA): 0.1226
• 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/G	rs2060476554	None	0.959	N	0.722	0.415	0.535152128566	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
E/K	None	None	0.116	N	0.298	0.164	0.315314060047	gnomAD-4.0.0	6.84396E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99638E-07	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	0.6174	likely_pathogenic	0.6454	pathogenic	-0.909	Destabilizing	0.959	D	0.661	neutral	N	0.512631919	None	None	N
E/C	0.9936	likely_pathogenic	0.9957	pathogenic	-0.433	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
E/D	0.5543	ambiguous	0.5671	pathogenic	-0.665	Destabilizing	0.828	D	0.567	neutral	N	0.513768069	None	None	N
E/F	0.992	likely_pathogenic	0.9953	pathogenic	-0.255	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
E/G	0.6077	likely_pathogenic	0.7281	pathogenic	-1.236	Destabilizing	0.959	D	0.722	prob.delet.	N	0.499527097	None	None	N
E/H	0.9661	likely_pathogenic	0.9773	pathogenic	-0.326	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	N
E/I	0.9542	likely_pathogenic	0.9643	pathogenic	-0.023	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
E/K	0.7961	likely_pathogenic	0.831	pathogenic	-0.245	Destabilizing	0.116	N	0.298	neutral	N	0.488120565	None	None	N
E/L	0.9526	likely_pathogenic	0.9633	pathogenic	-0.023	Destabilizing	0.984	D	0.737	prob.delet.	None	None	None	None	N
E/M	0.9467	likely_pathogenic	0.9567	pathogenic	0.283	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.8227	likely_pathogenic	0.8481	pathogenic	-0.802	Destabilizing	0.293	N	0.395	neutral	None	None	None	None	N
E/P	0.7941	likely_pathogenic	0.7974	pathogenic	-0.298	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
E/Q	0.6004	likely_pathogenic	0.6346	pathogenic	-0.687	Destabilizing	0.959	D	0.585	neutral	N	0.515955965	None	None	N
E/R	0.9164	likely_pathogenic	0.9372	pathogenic	0.068	Stabilizing	0.939	D	0.594	neutral	None	None	None	None	N
E/S	0.7787	likely_pathogenic	0.8186	pathogenic	-1.07	Destabilizing	0.969	D	0.59	neutral	None	None	None	None	N
E/T	0.8128	likely_pathogenic	0.8504	pathogenic	-0.788	Destabilizing	0.969	D	0.669	neutral	None	None	None	None	N
E/V	0.8607	likely_pathogenic	0.8833	pathogenic	-0.298	Destabilizing	0.994	D	0.736	prob.delet.	N	0.513862917	None	None	N
E/W	0.9985	likely_pathogenic	0.9993	pathogenic	0.1	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/Y	0.9869	likely_pathogenic	0.991	pathogenic	0.03	Stabilizing	0.999	D	0.765	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.