TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7405	22438;22439;22440	chr2:178722686;178722685;178722684	chr2:179587413;179587412;179587411
N2AB	7088	21487;21488;21489	chr2:178722686;178722685;178722684	chr2:179587413;179587412;179587411
N2A	6161	18706;18707;18708	chr2:178722686;178722685;178722684	chr2:179587413;179587412;179587411
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-58
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3567
• 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
S/F	rs794729627	None	None	N	0.397	0.145	0.479818277033	gnomAD-4.0.0	2.05445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73732E-04	1.79998E-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
S/A	0.0681	likely_benign	0.0692	benign	-0.632	Destabilizing	None	N	0.163	neutral	D	0.525613497	None	None	N
S/C	0.1087	likely_benign	0.1091	benign	-0.37	Destabilizing	0.295	N	0.522	neutral	N	0.520107775	None	None	N
S/D	0.2952	likely_benign	0.3739	ambiguous	0.376	Stabilizing	0.072	N	0.411	neutral	None	None	None	None	N
S/E	0.3397	likely_benign	0.3949	ambiguous	0.314	Stabilizing	0.072	N	0.417	neutral	None	None	None	None	N
S/F	0.0828	likely_benign	0.1001	benign	-1.007	Destabilizing	None	N	0.397	neutral	N	0.48832981	None	None	N
S/G	0.1342	likely_benign	0.1432	benign	-0.8	Destabilizing	0.016	N	0.355	neutral	None	None	None	None	N
S/H	0.2406	likely_benign	0.2626	benign	-1.207	Destabilizing	0.001	N	0.32	neutral	None	None	None	None	N
S/I	0.0925	likely_benign	0.0984	benign	-0.306	Destabilizing	0.013	N	0.517	neutral	None	None	None	None	N
S/K	0.4965	ambiguous	0.5663	pathogenic	-0.499	Destabilizing	0.072	N	0.409	neutral	None	None	None	None	N
S/L	0.0812	likely_benign	0.0811	benign	-0.306	Destabilizing	0.016	N	0.439	neutral	None	None	None	None	N
S/M	0.1522	likely_benign	0.1539	benign	-0.06	Destabilizing	0.214	N	0.531	neutral	None	None	None	None	N
S/N	0.1337	likely_benign	0.1381	benign	-0.251	Destabilizing	0.072	N	0.405	neutral	None	None	None	None	N
S/P	0.5449	ambiguous	0.6561	pathogenic	-0.384	Destabilizing	None	N	0.279	neutral	N	0.519600796	None	None	N
S/Q	0.3687	ambiguous	0.4051	ambiguous	-0.473	Destabilizing	0.356	N	0.497	neutral	None	None	None	None	N
S/R	0.4029	ambiguous	0.4733	ambiguous	-0.317	Destabilizing	0.072	N	0.567	neutral	None	None	None	None	N
S/T	0.0686	likely_benign	0.0668	benign	-0.41	Destabilizing	None	N	0.207	neutral	N	0.492324856	None	None	N
S/V	0.0937	likely_benign	0.099	benign	-0.384	Destabilizing	None	N	0.387	neutral	None	None	None	None	N
S/W	0.2063	likely_benign	0.262	benign	-0.939	Destabilizing	0.864	D	0.571	neutral	None	None	None	None	N
S/Y	0.0979	likely_benign	0.1136	benign	-0.694	Destabilizing	0.029	N	0.618	neutral	N	0.489570805	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.