TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5501	16726;16727;16728	chr2:178732560;178732559;178732558	chr2:179597287;179597286;179597285
N2AB	5184	15775;15776;15777	chr2:178732560;178732559;178732558	chr2:179597287;179597286;179597285
N2A	4257	12994;12995;12996	chr2:178732560;178732559;178732558	chr2:179597287;179597286;179597285
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-38
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.6944
• 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
E/K	None	None	0.013	N	0.162	0.245	0.32580497728	gnomAD-4.0.0	6.84262E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99489E-07	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
E/A	0.1264	likely_benign	0.1534	benign	-0.408	Destabilizing	0.505	D	0.427	neutral	D	0.530982031	None	None	N
E/C	0.8154	likely_pathogenic	0.8741	pathogenic	-0.032	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
E/D	0.0883	likely_benign	0.1095	benign	-0.409	Destabilizing	0.001	N	0.126	neutral	N	0.45738835	None	None	N
E/F	0.6502	likely_pathogenic	0.7542	pathogenic	-0.286	Destabilizing	0.967	D	0.527	neutral	None	None	None	None	N
E/G	0.0997	likely_benign	0.1247	benign	-0.606	Destabilizing	0.505	D	0.466	neutral	N	0.510300115	None	None	N
E/H	0.3735	ambiguous	0.4485	ambiguous	-0.065	Destabilizing	0.906	D	0.362	neutral	None	None	None	None	N
E/I	0.3494	ambiguous	0.4321	ambiguous	0.081	Stabilizing	0.906	D	0.532	neutral	None	None	None	None	N
E/K	0.1219	likely_benign	0.1498	benign	0.367	Stabilizing	0.013	N	0.162	neutral	N	0.491980926	None	None	N
E/L	0.3604	ambiguous	0.4515	ambiguous	0.081	Stabilizing	0.906	D	0.481	neutral	None	None	None	None	N
E/M	0.4077	ambiguous	0.4878	ambiguous	0.19	Stabilizing	0.991	D	0.528	neutral	None	None	None	None	N
E/N	0.1569	likely_benign	0.2104	benign	-0.008	Destabilizing	0.404	N	0.387	neutral	None	None	None	None	N
E/P	0.6865	likely_pathogenic	0.7714	pathogenic	-0.062	Destabilizing	0.906	D	0.423	neutral	None	None	None	None	N
E/Q	0.1352	likely_benign	0.1506	benign	0.024	Stabilizing	0.505	D	0.391	neutral	N	0.509163964	None	None	N
E/R	0.2197	likely_benign	0.2669	benign	0.553	Stabilizing	0.404	N	0.374	neutral	None	None	None	None	N
E/S	0.1521	likely_benign	0.1953	benign	-0.149	Destabilizing	0.404	N	0.381	neutral	None	None	None	None	N
E/T	0.1756	likely_benign	0.2116	benign	0.016	Stabilizing	0.575	D	0.439	neutral	None	None	None	None	N
E/V	0.1833	likely_benign	0.2217	benign	-0.062	Destabilizing	0.879	D	0.459	neutral	N	0.491203419	None	None	N
E/W	0.8289	likely_pathogenic	0.8908	pathogenic	-0.125	Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
E/Y	0.4983	ambiguous	0.6123	pathogenic	-0.036	Destabilizing	0.967	D	0.514	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.