TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6165	18718;18719;18720	chr2:178729760;178729759;178729758	chr2:179594487;179594486;179594485
N2AB	5848	17767;17768;17769	chr2:178729760;178729759;178729758	chr2:179594487;179594486;179594485
N2A	4921	14986;14987;14988	chr2:178729760;178729759;178729758	chr2:179594487;179594486;179594485
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-45
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.126
• 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
I/F	None	None	0.901	D	0.723	0.681	0.631006925375	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85853E-06	0	0
I/T	None	None	0.722	D	0.705	0.683	0.833457243385	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
I/V	rs886055296	None	0.001	D	0.28	0.257	0.630592674211	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85853E-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
I/A	0.6602	likely_pathogenic	0.6773	pathogenic	-2.635	Highly Destabilizing	0.415	N	0.709	prob.delet.	None	None	None	None	N
I/C	0.8342	likely_pathogenic	0.8317	pathogenic	-2.355	Highly Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
I/D	0.8846	likely_pathogenic	0.8938	pathogenic	-2.723	Highly Destabilizing	0.987	D	0.867	deleterious	None	None	None	None	N
I/E	0.8294	likely_pathogenic	0.8399	pathogenic	-2.437	Highly Destabilizing	0.961	D	0.855	deleterious	None	None	None	None	N
I/F	0.1669	likely_benign	0.1904	benign	-1.589	Destabilizing	0.901	D	0.723	prob.delet.	D	0.546022243	None	None	N
I/G	0.88	likely_pathogenic	0.8865	pathogenic	-3.252	Highly Destabilizing	0.961	D	0.841	deleterious	None	None	None	None	N
I/H	0.737	likely_pathogenic	0.7385	pathogenic	-2.756	Highly Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
I/K	0.7278	likely_pathogenic	0.7227	pathogenic	-1.969	Destabilizing	0.961	D	0.853	deleterious	None	None	None	None	N
I/L	0.1089	likely_benign	0.1066	benign	-0.818	Destabilizing	0.19	N	0.395	neutral	D	0.547689673	None	None	N
I/M	0.1248	likely_benign	0.1346	benign	-1.072	Destabilizing	0.901	D	0.693	prob.neutral	D	0.537957201	None	None	N
I/N	0.536	ambiguous	0.5501	ambiguous	-2.431	Highly Destabilizing	0.983	D	0.867	deleterious	D	0.640361454	None	None	N
I/P	0.934	likely_pathogenic	0.9401	pathogenic	-1.408	Destabilizing	0.987	D	0.867	deleterious	None	None	None	None	N
I/Q	0.7409	likely_pathogenic	0.7437	pathogenic	-2.17	Highly Destabilizing	0.987	D	0.863	deleterious	None	None	None	None	N
I/R	0.663	likely_pathogenic	0.654	pathogenic	-1.919	Destabilizing	0.961	D	0.865	deleterious	None	None	None	None	N
I/S	0.6413	likely_pathogenic	0.6558	pathogenic	-3.238	Highly Destabilizing	0.901	D	0.829	deleterious	D	0.640361454	None	None	N
I/T	0.6472	likely_pathogenic	0.6479	pathogenic	-2.769	Highly Destabilizing	0.722	D	0.705	prob.neutral	D	0.623938485	None	None	N
I/V	0.0965	likely_benign	0.1015	benign	-1.408	Destabilizing	0.001	N	0.28	neutral	D	0.552305994	None	None	N
I/W	0.8283	likely_pathogenic	0.8428	pathogenic	-1.875	Destabilizing	0.996	D	0.868	deleterious	None	None	None	None	N
I/Y	0.5495	ambiguous	0.5577	ambiguous	-1.635	Destabilizing	0.961	D	0.789	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.