TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7147	21664;21665;21666	chr2:178723661;178723660;178723659	chr2:179588388;179588387;179588386
N2AB	6830	20713;20714;20715	chr2:178723661;178723660;178723659	chr2:179588388;179588387;179588386
N2A	5903	17932;17933;17934	chr2:178723661;178723660;178723659	chr2:179588388;179588387;179588386
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-56
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7973
• Predicted PPI site: I

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
E/K	None	None	0.549	D	0.457	0.295	0.360565625551	gnomAD-4.0.0	3.23355E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89457E-06	0	3.0673E-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
E/A	0.156	likely_benign	0.1673	benign	-0.419	Destabilizing	0.004	N	0.269	neutral	D	0.526056214	None	None	I
E/C	0.8634	likely_pathogenic	0.8758	pathogenic	-0.373	Destabilizing	0.977	D	0.461	neutral	None	None	None	None	I
E/D	0.1187	likely_benign	0.1357	benign	-0.453	Destabilizing	0.002	N	0.121	neutral	N	0.488135331	None	None	I
E/F	0.72	likely_pathogenic	0.7349	pathogenic	0.089	Stabilizing	0.92	D	0.47	neutral	None	None	None	None	I
E/G	0.2315	likely_benign	0.2627	benign	-0.671	Destabilizing	0.379	N	0.449	neutral	D	0.533287733	None	None	I
E/H	0.447	ambiguous	0.4692	ambiguous	0.455	Stabilizing	0.92	D	0.44	neutral	None	None	None	None	I
E/I	0.3394	likely_benign	0.3575	ambiguous	0.231	Stabilizing	0.85	D	0.483	neutral	None	None	None	None	I
E/K	0.2092	likely_benign	0.221	benign	0.209	Stabilizing	0.549	D	0.457	neutral	D	0.528768445	None	None	I
E/L	0.372	ambiguous	0.396	ambiguous	0.231	Stabilizing	0.447	N	0.485	neutral	None	None	None	None	I
E/M	0.4459	ambiguous	0.4629	ambiguous	0.152	Stabilizing	0.992	D	0.449	neutral	None	None	None	None	I
E/N	0.2479	likely_benign	0.2698	benign	-0.426	Destabilizing	0.021	N	0.239	neutral	None	None	None	None	I
E/P	0.66	likely_pathogenic	0.7191	pathogenic	0.035	Stabilizing	0.92	D	0.485	neutral	None	None	None	None	I
E/Q	0.1603	likely_benign	0.164	benign	-0.325	Destabilizing	0.712	D	0.468	neutral	N	0.513108346	None	None	I
E/R	0.3151	likely_benign	0.3292	benign	0.6	Stabilizing	0.85	D	0.441	neutral	None	None	None	None	I
E/S	0.2038	likely_benign	0.2192	benign	-0.573	Destabilizing	0.059	N	0.232	neutral	None	None	None	None	I
E/T	0.2084	likely_benign	0.2162	benign	-0.349	Destabilizing	0.447	N	0.472	neutral	None	None	None	None	I
E/V	0.1791	likely_benign	0.185	benign	0.035	Stabilizing	0.379	N	0.481	neutral	N	0.51433771	None	None	I
E/W	0.8704	likely_pathogenic	0.88	pathogenic	0.352	Stabilizing	0.992	D	0.605	neutral	None	None	None	None	I
E/Y	0.5864	likely_pathogenic	0.6108	pathogenic	0.363	Stabilizing	0.972	D	0.473	neutral	None	None	None	None	I

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.