TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24504	73735;73736;73737	chr2:178572622;178572621;178572620	chr2:179437349;179437348;179437347
N2AB	22863	68812;68813;68814	chr2:178572622;178572621;178572620	chr2:179437349;179437348;179437347
N2A	21936	66031;66032;66033	chr2:178572622;178572621;178572620	chr2:179437349;179437348;179437347
N2B	15439	46540;46541;46542	chr2:178572622;178572621;178572620	chr2:179437349;179437348;179437347
Novex-1	15564	46915;46916;46917	chr2:178572622;178572621;178572620	chr2:179437349;179437348;179437347
Novex-2	15631	47116;47117;47118	chr2:178572622;178572621;178572620	chr2:179437349;179437348;179437347
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-132
• Domain position: 74
• Structural Position: 162
• Q(SASA): 0.8297
• 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
S/N	None	None	0.979	N	0.382	0.316	0.303123707472	gnomAD-4.0.0	1.59252E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43447E-05	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
S/A	0.0762	likely_benign	0.0693	benign	-0.226	Destabilizing	0.293	N	0.229	neutral	None	None	None	None	I
S/C	0.131	likely_benign	0.1133	benign	-0.311	Destabilizing	0.999	D	0.429	neutral	N	0.494587689	None	None	I
S/D	0.3845	ambiguous	0.3645	ambiguous	-0.096	Destabilizing	0.984	D	0.325	neutral	None	None	None	None	I
S/E	0.4564	ambiguous	0.4377	ambiguous	-0.211	Destabilizing	0.984	D	0.32	neutral	None	None	None	None	I
S/F	0.2938	likely_benign	0.2542	benign	-1.001	Destabilizing	0.995	D	0.426	neutral	None	None	None	None	I
S/G	0.0944	likely_benign	0.0854	benign	-0.249	Destabilizing	0.959	D	0.358	neutral	N	0.488458396	None	None	I
S/H	0.3508	ambiguous	0.3244	benign	-0.635	Destabilizing	1.0	D	0.414	neutral	None	None	None	None	I
S/I	0.1326	likely_benign	0.121	benign	-0.292	Destabilizing	0.921	D	0.385	neutral	D	0.539526944	None	None	I
S/K	0.5549	ambiguous	0.5132	ambiguous	-0.38	Destabilizing	0.984	D	0.34	neutral	None	None	None	None	I
S/L	0.1049	likely_benign	0.0954	benign	-0.292	Destabilizing	0.939	D	0.387	neutral	None	None	None	None	I
S/M	0.1926	likely_benign	0.1774	benign	-0.13	Destabilizing	0.995	D	0.405	neutral	None	None	None	None	I
S/N	0.128	likely_benign	0.121	benign	-0.108	Destabilizing	0.979	D	0.382	neutral	N	0.512340342	None	None	I
S/P	0.1378	likely_benign	0.1231	benign	-0.248	Destabilizing	0.088	N	0.358	neutral	None	None	None	None	I
S/Q	0.4148	ambiguous	0.3967	ambiguous	-0.359	Destabilizing	0.999	D	0.341	neutral	None	None	None	None	I
S/R	0.5346	ambiguous	0.4836	ambiguous	-0.149	Destabilizing	0.994	D	0.396	neutral	N	0.487697927	None	None	I
S/T	0.0787	likely_benign	0.0738	benign	-0.226	Destabilizing	0.238	N	0.373	neutral	N	0.512166984	None	None	I
S/V	0.1487	likely_benign	0.1362	benign	-0.248	Destabilizing	0.293	N	0.345	neutral	None	None	None	None	I
S/W	0.5262	ambiguous	0.4737	ambiguous	-1.078	Destabilizing	1.0	D	0.523	neutral	None	None	None	None	I
S/Y	0.286	likely_benign	0.266	benign	-0.77	Destabilizing	0.999	D	0.433	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.