TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17279	52060;52061;52062	chr2:178609475;178609474;178609473	chr2:179474202;179474201;179474200
N2AB	15638	47137;47138;47139	chr2:178609475;178609474;178609473	chr2:179474202;179474201;179474200
N2A	14711	44356;44357;44358	chr2:178609475;178609474;178609473	chr2:179474202;179474201;179474200
N2B	8214	24865;24866;24867	chr2:178609475;178609474;178609473	chr2:179474202;179474201;179474200
Novex-1	8339	25240;25241;25242	chr2:178609475;178609474;178609473	chr2:179474202;179474201;179474200
Novex-2	8406	25441;25442;25443	chr2:178609475;178609474;178609473	chr2:179474202;179474201;179474200
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-112
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.156
• 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/T	None	None	0.722	D	0.712	0.667	0.839211880287	gnomAD-4.0.0	3.18798E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72551E-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	0.7337	likely_pathogenic	0.7566	pathogenic	-2.086	Highly Destabilizing	0.775	D	0.67	neutral	None	None	None	None	N
I/C	0.8705	likely_pathogenic	0.8713	pathogenic	-1.292	Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
I/D	0.9912	likely_pathogenic	0.9919	pathogenic	-1.652	Destabilizing	0.987	D	0.872	deleterious	None	None	None	None	N
I/E	0.9647	likely_pathogenic	0.965	pathogenic	-1.552	Destabilizing	0.961	D	0.866	deleterious	None	None	None	None	N
I/F	0.5591	ambiguous	0.549	ambiguous	-1.274	Destabilizing	0.82	D	0.672	neutral	N	0.503794855	None	None	N
I/G	0.968	likely_pathogenic	0.9692	pathogenic	-2.517	Highly Destabilizing	0.961	D	0.856	deleterious	None	None	None	None	N
I/H	0.9604	likely_pathogenic	0.9602	pathogenic	-1.673	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
I/K	0.9072	likely_pathogenic	0.8986	pathogenic	-1.577	Destabilizing	0.961	D	0.866	deleterious	None	None	None	None	N
I/L	0.3034	likely_benign	0.2944	benign	-0.916	Destabilizing	0.003	N	0.233	neutral	N	0.502273918	None	None	N
I/M	0.2645	likely_benign	0.2666	benign	-0.725	Destabilizing	0.901	D	0.645	neutral	D	0.531306859	None	None	N
I/N	0.9051	likely_pathogenic	0.9176	pathogenic	-1.547	Destabilizing	0.983	D	0.869	deleterious	D	0.531813838	None	None	N
I/P	0.9635	likely_pathogenic	0.9598	pathogenic	-1.279	Destabilizing	0.987	D	0.874	deleterious	None	None	None	None	N
I/Q	0.9325	likely_pathogenic	0.9309	pathogenic	-1.591	Destabilizing	0.987	D	0.885	deleterious	None	None	None	None	N
I/R	0.8828	likely_pathogenic	0.8724	pathogenic	-1.063	Destabilizing	0.961	D	0.869	deleterious	None	None	None	None	N
I/S	0.8532	likely_pathogenic	0.878	pathogenic	-2.235	Highly Destabilizing	0.949	D	0.793	deleterious	N	0.513456093	None	None	N
I/T	0.7165	likely_pathogenic	0.7416	pathogenic	-1.999	Destabilizing	0.722	D	0.712	prob.delet.	D	0.531306859	None	None	N
I/V	0.0834	likely_benign	0.0808	benign	-1.279	Destabilizing	0.034	N	0.149	neutral	N	0.451222021	None	None	N
I/W	0.9794	likely_pathogenic	0.9766	pathogenic	-1.44	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
I/Y	0.9136	likely_pathogenic	0.9102	pathogenic	-1.211	Destabilizing	0.961	D	0.719	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.