TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9049	27370;27371;27372	chr2:178712880;178712879;178712878	chr2:179577607;179577606;179577605
N2AB	8732	26419;26420;26421	chr2:178712880;178712879;178712878	chr2:179577607;179577606;179577605
N2A	7805	23638;23639;23640	chr2:178712880;178712879;178712878	chr2:179577607;179577606;179577605
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-76
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.5436
• 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
S/G	None	None	0.007	N	0.231	0.222	0.301122078929	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.0748	likely_benign	0.0782	benign	-0.404	Destabilizing	0.004	N	0.199	neutral	None	None	None	None	I
S/C	0.1302	likely_benign	0.144	benign	-0.411	Destabilizing	0.196	N	0.417	neutral	N	0.517349525	None	None	I
S/D	0.1923	likely_benign	0.2071	benign	0.586	Stabilizing	None	N	0.096	neutral	None	None	None	None	I
S/E	0.2574	likely_benign	0.2702	benign	0.533	Stabilizing	None	N	0.097	neutral	None	None	None	None	I
S/F	0.1473	likely_benign	0.1468	benign	-0.934	Destabilizing	None	N	0.323	neutral	None	None	None	None	I
S/G	0.0941	likely_benign	0.1029	benign	-0.551	Destabilizing	0.007	N	0.231	neutral	N	0.498231312	None	None	I
S/H	0.1377	likely_benign	0.1478	benign	-0.973	Destabilizing	0.245	N	0.425	neutral	None	None	None	None	I
S/I	0.1009	likely_benign	0.1062	benign	-0.143	Destabilizing	None	N	0.339	neutral	D	0.537948076	None	None	I
S/K	0.2237	likely_benign	0.239	benign	-0.272	Destabilizing	None	N	0.084	neutral	None	None	None	None	I
S/L	0.0848	likely_benign	0.0846	benign	-0.143	Destabilizing	0.009	N	0.308	neutral	None	None	None	None	I
S/M	0.1517	likely_benign	0.1468	benign	-0.121	Destabilizing	0.245	N	0.427	neutral	None	None	None	None	I
S/N	0.0832	likely_benign	0.0884	benign	-0.176	Destabilizing	None	N	0.064	neutral	N	0.479785207	None	None	I
S/P	0.5559	ambiguous	0.616	pathogenic	-0.199	Destabilizing	0.085	N	0.449	neutral	None	None	None	None	I
S/Q	0.2193	likely_benign	0.2336	benign	-0.299	Destabilizing	0.022	N	0.277	neutral	None	None	None	None	I
S/R	0.1764	likely_benign	0.1888	benign	-0.196	Destabilizing	0.017	N	0.406	neutral	N	0.519746317	None	None	I
S/T	0.059	likely_benign	0.0622	benign	-0.274	Destabilizing	None	N	0.118	neutral	N	0.446960712	None	None	I
S/V	0.1162	likely_benign	0.1207	benign	-0.199	Destabilizing	0.009	N	0.321	neutral	None	None	None	None	I
S/W	0.2506	likely_benign	0.2571	benign	-0.946	Destabilizing	0.788	D	0.487	neutral	None	None	None	None	I
S/Y	0.1221	likely_benign	0.1264	benign	-0.631	Destabilizing	0.022	N	0.572	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.