TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5428	16507;16508;16509	chr2:178732894;178732893;178732892	chr2:179597621;179597620;179597619
N2AB	5111	15556;15557;15558	chr2:178732894;178732893;178732892	chr2:179597621;179597620;179597619
N2A	4184	12775;12776;12777	chr2:178732894;178732893;178732892	chr2:179597621;179597620;179597619
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-37
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1944
• 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
T/A	None	None	0.047	N	0.371	0.198	0.186928172975	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86005E-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
T/A	0.1214	likely_benign	0.1081	benign	-1.375	Destabilizing	0.047	N	0.371	neutral	N	0.499501629	None	None	N
T/C	0.4402	ambiguous	0.4048	ambiguous	-0.954	Destabilizing	0.983	D	0.607	neutral	None	None	None	None	N
T/D	0.624	likely_pathogenic	0.6099	pathogenic	-1.504	Destabilizing	0.418	N	0.569	neutral	None	None	None	None	N
T/E	0.4959	ambiguous	0.5293	ambiguous	-1.283	Destabilizing	0.418	N	0.557	neutral	None	None	None	None	N
T/F	0.2438	likely_benign	0.2362	benign	-1.128	Destabilizing	0.716	D	0.624	neutral	None	None	None	None	N
T/G	0.4254	ambiguous	0.3587	ambiguous	-1.776	Destabilizing	0.264	N	0.595	neutral	None	None	None	None	N
T/H	0.2665	likely_benign	0.2585	benign	-1.758	Destabilizing	0.836	D	0.636	neutral	None	None	None	None	N
T/I	0.1429	likely_benign	0.1483	benign	-0.306	Destabilizing	0.002	N	0.471	neutral	N	0.479244553	None	None	N
T/K	0.3434	ambiguous	0.3584	ambiguous	-0.242	Destabilizing	0.004	N	0.395	neutral	None	None	None	None	N
T/L	0.1276	likely_benign	0.1234	benign	-0.306	Destabilizing	0.061	N	0.475	neutral	None	None	None	None	N
T/M	0.1171	likely_benign	0.1188	benign	-0.357	Destabilizing	0.061	N	0.479	neutral	None	None	None	None	N
T/N	0.2002	likely_benign	0.1855	benign	-0.979	Destabilizing	0.213	N	0.535	neutral	N	0.518619842	None	None	N
T/P	0.7976	likely_pathogenic	0.7676	pathogenic	-0.634	Destabilizing	0.794	D	0.603	neutral	D	0.530229637	None	None	N
T/Q	0.2963	likely_benign	0.3038	benign	-0.773	Destabilizing	0.716	D	0.607	neutral	None	None	None	None	N
T/R	0.2257	likely_benign	0.2346	benign	-0.492	Destabilizing	0.264	N	0.567	neutral	None	None	None	None	N
T/S	0.1173	likely_benign	0.1034	benign	-1.273	Destabilizing	0.007	N	0.309	neutral	N	0.515739567	None	None	N
T/V	0.1382	likely_benign	0.1429	benign	-0.634	Destabilizing	0.01	N	0.27	neutral	None	None	None	None	N
T/W	0.6109	likely_pathogenic	0.6072	pathogenic	-1.208	Destabilizing	0.983	D	0.677	prob.neutral	None	None	None	None	N
T/Y	0.3137	likely_benign	0.2989	benign	-0.831	Destabilizing	0.94	D	0.619	neutral	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.