TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28207	84844;84845;84846	chr2:178561513;178561512;178561511	chr2:179426240;179426239;179426238
N2AB	26566	79921;79922;79923	chr2:178561513;178561512;178561511	chr2:179426240;179426239;179426238
N2A	25639	77140;77141;77142	chr2:178561513;178561512;178561511	chr2:179426240;179426239;179426238
N2B	19142	57649;57650;57651	chr2:178561513;178561512;178561511	chr2:179426240;179426239;179426238
Novex-1	19267	58024;58025;58026	chr2:178561513;178561512;178561511	chr2:179426240;179426239;179426238
Novex-2	19334	58225;58226;58227	chr2:178561513;178561512;178561511	chr2:179426240;179426239;179426238
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-93
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.6708
• 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
I/N	None	None	0.017	N	0.371	0.07	0.264547087235	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.1236	likely_benign	0.1164	benign	-0.483	Destabilizing	0.002	N	0.225	neutral	None	None	None	None	I
I/C	0.293	likely_benign	0.2835	benign	-0.74	Destabilizing	0.245	N	0.197	neutral	None	None	None	None	I
I/D	0.4018	ambiguous	0.4043	ambiguous	-0.262	Destabilizing	0.044	N	0.351	neutral	None	None	None	None	I
I/E	0.3771	ambiguous	0.3753	ambiguous	-0.348	Destabilizing	0.018	N	0.325	neutral	None	None	None	None	I
I/F	0.0944	likely_benign	0.0957	benign	-0.608	Destabilizing	0.017	N	0.198	neutral	N	0.466452471	None	None	I
I/G	0.2425	likely_benign	0.2174	benign	-0.592	Destabilizing	None	N	0.148	neutral	None	None	None	None	I
I/H	0.2167	likely_benign	0.2259	benign	0.107	Stabilizing	0.245	N	0.243	neutral	None	None	None	None	I
I/K	0.254	likely_benign	0.2583	benign	-0.334	Destabilizing	0.009	N	0.3	neutral	None	None	None	None	I
I/L	0.0718	likely_benign	0.069	benign	-0.313	Destabilizing	None	N	0.111	neutral	N	0.431953108	None	None	I
I/M	0.0604	likely_benign	0.0559	benign	-0.607	Destabilizing	None	N	0.179	neutral	N	0.445501196	None	None	I
I/N	0.0846	likely_benign	0.0853	benign	-0.21	Destabilizing	0.017	N	0.371	neutral	N	0.441114096	None	None	I
I/P	0.573	likely_pathogenic	0.558	ambiguous	-0.341	Destabilizing	0.085	N	0.385	neutral	None	None	None	None	I
I/Q	0.2131	likely_benign	0.2061	benign	-0.387	Destabilizing	0.044	N	0.383	neutral	None	None	None	None	I
I/R	0.2002	likely_benign	0.2134	benign	0.144	Stabilizing	0.044	N	0.393	neutral	None	None	None	None	I
I/S	0.088	likely_benign	0.0861	benign	-0.588	Destabilizing	None	N	0.111	neutral	N	0.412658059	None	None	I
I/T	0.0822	likely_benign	0.0854	benign	-0.574	Destabilizing	None	N	0.105	neutral	N	0.366442979	None	None	I
I/V	0.0662	likely_benign	0.0646	benign	-0.341	Destabilizing	None	N	0.113	neutral	N	0.433318545	None	None	I
I/W	0.5544	ambiguous	0.5157	ambiguous	-0.629	Destabilizing	0.788	D	0.235	neutral	None	None	None	None	I
I/Y	0.2296	likely_benign	0.2299	benign	-0.396	Destabilizing	0.085	N	0.325	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.