TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3173	9742;9743;9744	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292
N2AB	3173	9742;9743;9744	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292
N2A	3173	9742;9743;9744	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292
N2B	3127	9604;9605;9606	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292
Novex-1	3127	9604;9605;9606	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292
Novex-2	3127	9604;9605;9606	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292
Novex-3	3173	9742;9743;9744	chr2:178766567;178766566;178766565	chr2:179631294;179631293;179631292

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-22
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.5798
• 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
D/E	rs151129843	None	0.092	N	0.359	0.068	0.0297737177859	gnomAD-4.0.0	5.47288E-06	None	None	None	None	N	None	2.98686E-05	0	None	0	0	None	0	0	8.99308E-07	0	9.93608E-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
D/A	0.7635	likely_pathogenic	0.6734	pathogenic	-0.252	Destabilizing	0.957	D	0.689	prob.neutral	N	0.328188656	None	None	N
D/C	0.9889	likely_pathogenic	0.9844	pathogenic	0.011	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
D/E	0.5847	likely_pathogenic	0.454	ambiguous	-0.437	Destabilizing	0.092	N	0.359	neutral	N	0.348350273	None	None	N
D/F	0.9659	likely_pathogenic	0.9615	pathogenic	-0.238	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
D/G	0.7706	likely_pathogenic	0.7193	pathogenic	-0.468	Destabilizing	0.928	D	0.698	prob.neutral	N	0.39227628	None	None	N
D/H	0.9284	likely_pathogenic	0.9048	pathogenic	-0.249	Destabilizing	0.997	D	0.743	deleterious	N	0.356999686	None	None	N
D/I	0.9263	likely_pathogenic	0.9139	pathogenic	0.274	Stabilizing	0.992	D	0.777	deleterious	None	None	None	None	N
D/K	0.9355	likely_pathogenic	0.9157	pathogenic	0.118	Stabilizing	0.968	D	0.689	prob.neutral	None	None	None	None	N
D/L	0.9064	likely_pathogenic	0.877	pathogenic	0.274	Stabilizing	0.983	D	0.751	deleterious	None	None	None	None	N
D/M	0.9631	likely_pathogenic	0.9582	pathogenic	0.428	Stabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
D/N	0.5053	ambiguous	0.4232	ambiguous	-0.087	Destabilizing	0.978	D	0.742	deleterious	N	0.39227628	None	None	N
D/P	0.9662	likely_pathogenic	0.9183	pathogenic	0.122	Stabilizing	0.992	D	0.744	deleterious	None	None	None	None	N
D/Q	0.9346	likely_pathogenic	0.9093	pathogenic	-0.063	Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
D/R	0.9484	likely_pathogenic	0.9312	pathogenic	0.259	Stabilizing	0.983	D	0.769	deleterious	None	None	None	None	N
D/S	0.6774	likely_pathogenic	0.5859	pathogenic	-0.22	Destabilizing	0.895	D	0.719	prob.delet.	None	None	None	None	N
D/T	0.8466	likely_pathogenic	0.8054	pathogenic	-0.062	Destabilizing	0.983	D	0.733	prob.delet.	None	None	None	None	N
D/V	0.8197	likely_pathogenic	0.7839	pathogenic	0.122	Stabilizing	0.978	D	0.75	deleterious	N	0.356713365	None	None	N
D/W	0.9905	likely_pathogenic	0.99	pathogenic	-0.145	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
D/Y	0.8159	likely_pathogenic	0.786	pathogenic	-0.018	Destabilizing	0.999	D	0.765	deleterious	N	0.393404294	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.