TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4850	14773;14774;14775	chr2:178735898;178735897;178735896	chr2:179600625;179600624;179600623
N2AB	4533	13822;13823;13824	chr2:178735898;178735897;178735896	chr2:179600625;179600624;179600623
N2A	3606	11041;11042;11043	chr2:178735898;178735897;178735896	chr2:179600625;179600624;179600623
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-31
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1085
• 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/L	rs760092355	-0.521	0.92	N	0.756	0.29	0.318828661733	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/L	rs760092355	-0.521	0.92	N	0.756	0.29	0.318828661733	gnomAD-4.0.0	2.73675E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63725E-05	0
H/R	None	None	0.959	N	0.738	0.323	0.195762928549	gnomAD-4.0.0	1.36838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31863E-05	0
H/Y	None	None	0.061	N	0.356	0.284	0.136095386433	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
H/A	0.6513	likely_pathogenic	0.559	ambiguous	-1.345	Destabilizing	0.863	D	0.751	deleterious	None	None	None	None	N
H/C	0.3289	likely_benign	0.2738	benign	-0.764	Destabilizing	0.046	N	0.739	prob.delet.	None	None	None	None	N
H/D	0.7341	likely_pathogenic	0.6446	pathogenic	-1.265	Destabilizing	0.986	D	0.765	deleterious	N	0.451338306	None	None	N
H/E	0.77	likely_pathogenic	0.6606	pathogenic	-1.122	Destabilizing	0.99	D	0.699	prob.neutral	None	None	None	None	N
H/F	0.5441	ambiguous	0.4578	ambiguous	0.149	Stabilizing	0.884	D	0.747	deleterious	None	None	None	None	N
H/G	0.7116	likely_pathogenic	0.6251	pathogenic	-1.73	Destabilizing	0.969	D	0.755	deleterious	None	None	None	None	N
H/I	0.6521	likely_pathogenic	0.5383	ambiguous	-0.243	Destabilizing	0.969	D	0.807	deleterious	None	None	None	None	N
H/K	0.607	likely_pathogenic	0.4779	ambiguous	-1.069	Destabilizing	0.969	D	0.754	deleterious	None	None	None	None	N
H/L	0.3419	ambiguous	0.2668	benign	-0.243	Destabilizing	0.92	D	0.756	deleterious	N	0.447529795	None	None	N
H/M	0.766	likely_pathogenic	0.6827	pathogenic	-0.461	Destabilizing	0.997	D	0.742	deleterious	None	None	None	None	N
H/N	0.2836	likely_benign	0.2266	benign	-1.37	Destabilizing	0.986	D	0.707	prob.neutral	N	0.453458555	None	None	N
H/P	0.8208	likely_pathogenic	0.689	pathogenic	-0.595	Destabilizing	0.996	D	0.775	deleterious	N	0.44018006	None	None	N
H/Q	0.457	ambiguous	0.3414	ambiguous	-1.024	Destabilizing	0.996	D	0.749	deleterious	N	0.450521399	None	None	N
H/R	0.296	likely_benign	0.2037	benign	-1.349	Destabilizing	0.959	D	0.738	prob.delet.	N	0.450896776	None	None	N
H/S	0.5656	likely_pathogenic	0.4866	ambiguous	-1.487	Destabilizing	0.969	D	0.749	deleterious	None	None	None	None	N
H/T	0.661	likely_pathogenic	0.5508	ambiguous	-1.238	Destabilizing	0.969	D	0.753	deleterious	None	None	None	None	N
H/V	0.5804	likely_pathogenic	0.4642	ambiguous	-0.595	Destabilizing	0.939	D	0.772	deleterious	None	None	None	None	N
H/W	0.6857	likely_pathogenic	0.5985	pathogenic	0.489	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
H/Y	0.1659	likely_benign	0.1358	benign	0.506	Stabilizing	0.061	N	0.356	neutral	N	0.423630029	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.