TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28190	84793;84794;84795	chr2:178561564;178561563;178561562	chr2:179426291;179426290;179426289
N2AB	26549	79870;79871;79872	chr2:178561564;178561563;178561562	chr2:179426291;179426290;179426289
N2A	25622	77089;77090;77091	chr2:178561564;178561563;178561562	chr2:179426291;179426290;179426289
N2B	19125	57598;57599;57600	chr2:178561564;178561563;178561562	chr2:179426291;179426290;179426289
Novex-1	19250	57973;57974;57975	chr2:178561564;178561563;178561562	chr2:179426291;179426290;179426289
Novex-2	19317	58174;58175;58176	chr2:178561564;178561563;178561562	chr2:179426291;179426290;179426289
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-93
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1486
• 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
H/P	None	None	0.99	N	0.765	0.556	0.589665606642	gnomAD-4.0.0	1.59244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85981E-06	0	0
H/Q	None	None	0.97	N	0.719	0.325	0.348983352498	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
H/R	rs1248103386	-1.544	0.97	N	0.719	0.48	0.383089235449	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
H/R	rs1248103386	-1.544	0.97	N	0.719	0.48	0.383089235449	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/R	rs1248103386	-1.544	0.97	N	0.719	0.48	0.383089235449	gnomAD-4.0.0	2.56354E-06	None	None	None	None	N	None	1.69102E-05	0	None	0	2.43049E-05	None	0	0	0	0	0
H/Y	rs770757137	0.17	0.014	N	0.47	0.374	0.257292322809	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
H/Y	rs770757137	0.17	0.014	N	0.47	0.374	0.257292322809	gnomAD-4.0.0	1.59256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02572E-05

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
H/A	0.9634	likely_pathogenic	0.9559	pathogenic	-2.059	Highly Destabilizing	0.86	D	0.702	prob.neutral	None	None	None	None	N
H/C	0.6113	likely_pathogenic	0.5884	pathogenic	-1.156	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
H/D	0.9701	likely_pathogenic	0.9623	pathogenic	-2.055	Highly Destabilizing	0.99	D	0.725	prob.delet.	N	0.471720725	None	None	N
H/E	0.9516	likely_pathogenic	0.9402	pathogenic	-1.86	Destabilizing	0.926	D	0.671	neutral	None	None	None	None	N
H/F	0.6362	likely_pathogenic	0.6441	pathogenic	-0.037	Destabilizing	0.915	D	0.725	prob.delet.	None	None	None	None	N
H/G	0.979	likely_pathogenic	0.9718	pathogenic	-2.447	Highly Destabilizing	0.926	D	0.714	prob.delet.	None	None	None	None	N
H/I	0.7741	likely_pathogenic	0.7674	pathogenic	-0.891	Destabilizing	0.956	D	0.799	deleterious	None	None	None	None	N
H/K	0.8964	likely_pathogenic	0.8669	pathogenic	-1.554	Destabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	N
H/L	0.5806	likely_pathogenic	0.5668	pathogenic	-0.891	Destabilizing	0.698	D	0.755	deleterious	N	0.488579969	None	None	N
H/M	0.9173	likely_pathogenic	0.9098	pathogenic	-1.023	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
H/N	0.6557	likely_pathogenic	0.6064	pathogenic	-2.164	Highly Destabilizing	0.904	D	0.662	neutral	N	0.511936832	None	None	N
H/P	0.9916	likely_pathogenic	0.9888	pathogenic	-1.274	Destabilizing	0.99	D	0.765	deleterious	N	0.503120296	None	None	N
H/Q	0.8128	likely_pathogenic	0.7778	pathogenic	-1.727	Destabilizing	0.97	D	0.719	prob.delet.	N	0.515707855	None	None	N
H/R	0.5705	likely_pathogenic	0.5081	ambiguous	-1.815	Destabilizing	0.97	D	0.719	prob.delet.	N	0.504258711	None	None	N
H/S	0.8972	likely_pathogenic	0.8802	pathogenic	-2.25	Highly Destabilizing	0.926	D	0.713	prob.delet.	None	None	None	None	N
H/T	0.914	likely_pathogenic	0.9012	pathogenic	-1.952	Destabilizing	0.978	D	0.71	prob.delet.	None	None	None	None	N
H/V	0.7916	likely_pathogenic	0.7832	pathogenic	-1.274	Destabilizing	0.956	D	0.766	deleterious	None	None	None	None	N
H/W	0.5804	likely_pathogenic	0.5906	pathogenic	0.474	Stabilizing	0.994	D	0.751	deleterious	None	None	None	None	N
H/Y	0.2482	likely_benign	0.2537	benign	0.199	Stabilizing	0.014	N	0.47	neutral	N	0.474632024	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.