TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5134	15625;15626;15627	chr2:178734424;178734423;178734422	chr2:179599151;179599150;179599149
N2AB	4817	14674;14675;14676	chr2:178734424;178734423;178734422	chr2:179599151;179599150;179599149
N2A	3890	11893;11894;11895	chr2:178734424;178734423;178734422	chr2:179599151;179599150;179599149
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-34
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0407
• 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	rs1362573029	-2.54	0.722	D	0.732	0.752	0.820698191142	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/T	rs1362573029	-2.54	0.722	D	0.732	0.752	0.820698191142	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1362573029	-2.54	0.722	D	0.732	0.752	0.820698191142	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46959E-05	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	0.9058	likely_pathogenic	0.9356	pathogenic	-2.825	Highly Destabilizing	0.633	D	0.687	prob.neutral	None	None	None	None	N
I/C	0.9094	likely_pathogenic	0.9424	pathogenic	-1.725	Destabilizing	0.989	D	0.765	deleterious	None	None	None	None	N
I/D	0.9937	likely_pathogenic	0.9956	pathogenic	-3.314	Highly Destabilizing	0.987	D	0.845	deleterious	None	None	None	None	N
I/E	0.9925	likely_pathogenic	0.9946	pathogenic	-3.005	Highly Destabilizing	0.961	D	0.845	deleterious	None	None	None	None	N
I/F	0.3847	ambiguous	0.4275	ambiguous	-1.624	Destabilizing	0.018	N	0.352	neutral	D	0.621038261	None	None	N
I/G	0.978	likely_pathogenic	0.9845	pathogenic	-3.394	Highly Destabilizing	0.961	D	0.821	deleterious	None	None	None	None	N
I/H	0.9769	likely_pathogenic	0.9847	pathogenic	-3.058	Highly Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
I/K	0.9847	likely_pathogenic	0.9879	pathogenic	-1.944	Destabilizing	0.961	D	0.844	deleterious	None	None	None	None	N
I/L	0.2586	likely_benign	0.2917	benign	-1.102	Destabilizing	0.19	N	0.442	neutral	D	0.614444363	None	None	N
I/M	0.2734	likely_benign	0.3271	benign	-1.251	Destabilizing	0.901	D	0.687	prob.neutral	D	0.761404987	None	None	N
I/N	0.907	likely_pathogenic	0.9346	pathogenic	-2.598	Highly Destabilizing	0.983	D	0.843	deleterious	D	0.827968712	None	None	N
I/P	0.9904	likely_pathogenic	0.9938	pathogenic	-1.67	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
I/Q	0.9831	likely_pathogenic	0.9883	pathogenic	-2.254	Highly Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	N
I/R	0.9771	likely_pathogenic	0.9804	pathogenic	-2.007	Highly Destabilizing	0.961	D	0.843	deleterious	None	None	None	None	N
I/S	0.9283	likely_pathogenic	0.9503	pathogenic	-3.1	Highly Destabilizing	0.901	D	0.78	deleterious	D	0.827968712	None	None	N
I/T	0.9269	likely_pathogenic	0.9493	pathogenic	-2.643	Highly Destabilizing	0.722	D	0.732	prob.delet.	D	0.828194521	None	None	N
I/V	0.1087	likely_benign	0.1134	benign	-1.67	Destabilizing	0.003	N	0.283	neutral	D	0.573037433	None	None	N
I/W	0.9775	likely_pathogenic	0.9838	pathogenic	-2.004	Highly Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
I/Y	0.8754	likely_pathogenic	0.8921	pathogenic	-1.854	Destabilizing	0.858	D	0.753	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.