TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8088	24487;24488;24489	chr2:178718938;178718937;178718936	chr2:179583665;179583664;179583663
N2AB	7771	23536;23537;23538	chr2:178718938;178718937;178718936	chr2:179583665;179583664;179583663
N2A	6844	20755;20756;20757	chr2:178718938;178718937;178718936	chr2:179583665;179583664;179583663
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-66
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7458
• 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/G	None	None	0.669	N	0.492	0.393	0.501371821861	gnomAD-4.0.0	6.85347E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.004E-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	0.1633	likely_benign	0.1807	benign	-0.465	Destabilizing	0.051	N	0.245	neutral	N	0.521746472	None	None	I
E/C	0.8792	likely_pathogenic	0.9042	pathogenic	-0.338	Destabilizing	0.998	D	0.471	neutral	None	None	None	None	I
E/D	0.1429	likely_benign	0.1618	benign	-0.475	Destabilizing	0.012	N	0.237	neutral	N	0.503758144	None	None	I
E/F	0.7671	likely_pathogenic	0.8118	pathogenic	0.126	Stabilizing	0.974	D	0.48	neutral	None	None	None	None	I
E/G	0.2786	likely_benign	0.2963	benign	-0.738	Destabilizing	0.669	D	0.492	neutral	N	0.514360557	None	None	I
E/H	0.4935	ambiguous	0.5654	pathogenic	0.421	Stabilizing	0.998	D	0.457	neutral	None	None	None	None	I
E/I	0.3829	ambiguous	0.4527	ambiguous	0.251	Stabilizing	0.904	D	0.477	neutral	None	None	None	None	I
E/K	0.1921	likely_benign	0.2311	benign	0.259	Stabilizing	0.801	D	0.523	neutral	N	0.485074127	None	None	I
E/L	0.4306	ambiguous	0.5055	ambiguous	0.251	Stabilizing	0.728	D	0.5	neutral	None	None	None	None	I
E/M	0.4411	ambiguous	0.4895	ambiguous	0.23	Stabilizing	0.993	D	0.467	neutral	None	None	None	None	I
E/N	0.2702	likely_benign	0.3263	benign	-0.469	Destabilizing	0.728	D	0.477	neutral	None	None	None	None	I
E/P	0.7201	likely_pathogenic	0.7927	pathogenic	0.033	Stabilizing	0.974	D	0.497	neutral	None	None	None	None	I
E/Q	0.1535	likely_benign	0.1791	benign	-0.349	Destabilizing	0.966	D	0.491	neutral	N	0.511222834	None	None	I
E/R	0.3169	likely_benign	0.3726	ambiguous	0.624	Stabilizing	0.974	D	0.479	neutral	None	None	None	None	I
E/S	0.2048	likely_benign	0.2374	benign	-0.609	Destabilizing	0.172	N	0.261	neutral	None	None	None	None	I
E/T	0.2029	likely_benign	0.238	benign	-0.362	Destabilizing	0.728	D	0.491	neutral	None	None	None	None	I
E/V	0.2004	likely_benign	0.2396	benign	0.033	Stabilizing	0.111	N	0.323	neutral	N	0.510297328	None	None	I
E/W	0.9051	likely_pathogenic	0.9294	pathogenic	0.423	Stabilizing	0.998	D	0.618	neutral	None	None	None	None	I
E/Y	0.6699	likely_pathogenic	0.7293	pathogenic	0.412	Stabilizing	0.991	D	0.487	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.