TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22335	67228;67229;67230	chr2:178580376;178580375;178580374	chr2:179445103;179445102;179445101
N2AB	20694	62305;62306;62307	chr2:178580376;178580375;178580374	chr2:179445103;179445102;179445101
N2A	19767	59524;59525;59526	chr2:178580376;178580375;178580374	chr2:179445103;179445102;179445101
N2B	13270	40033;40034;40035	chr2:178580376;178580375;178580374	chr2:179445103;179445102;179445101
Novex-1	13395	40408;40409;40410	chr2:178580376;178580375;178580374	chr2:179445103;179445102;179445101
Novex-2	13462	40609;40610;40611	chr2:178580376;178580375;178580374	chr2:179445103;179445102;179445101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-126
• Domain position: 71
• Structural Position: 157
• Q(SASA): 0.1748
• 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
T/I	None	None	0.82	N	0.645	0.174	0.40318662893	gnomAD-4.0.0	1.59251E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86064E-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	0.1122	likely_benign	0.1098	benign	-1.09	Destabilizing	0.349	N	0.509	neutral	N	0.488201225	None	None	I
T/C	0.3336	likely_benign	0.3295	benign	-0.956	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	I
T/D	0.614	likely_pathogenic	0.6175	pathogenic	-1.345	Destabilizing	0.633	D	0.62	neutral	None	None	None	None	I
T/E	0.3866	ambiguous	0.379	ambiguous	-1.183	Destabilizing	0.775	D	0.623	neutral	None	None	None	None	I
T/F	0.2492	likely_benign	0.2532	benign	-0.676	Destabilizing	0.923	D	0.741	deleterious	None	None	None	None	I
T/G	0.3595	ambiguous	0.3659	ambiguous	-1.486	Destabilizing	0.633	D	0.654	neutral	None	None	None	None	I
T/H	0.2137	likely_benign	0.2185	benign	-1.613	Destabilizing	0.989	D	0.714	prob.delet.	None	None	None	None	I
T/I	0.1578	likely_benign	0.1589	benign	-0.069	Destabilizing	0.82	D	0.645	neutral	N	0.506758377	None	None	I
T/K	0.2342	likely_benign	0.2445	benign	-0.842	Destabilizing	0.633	D	0.623	neutral	None	None	None	None	I
T/L	0.1177	likely_benign	0.1149	benign	-0.069	Destabilizing	0.633	D	0.575	neutral	None	None	None	None	I
T/M	0.1081	likely_benign	0.0997	benign	-0.125	Destabilizing	0.415	N	0.55	neutral	None	None	None	None	I
T/N	0.162	likely_benign	0.1672	benign	-1.356	Destabilizing	0.018	N	0.379	neutral	N	0.4968881	None	None	I
T/P	0.8367	likely_pathogenic	0.8526	pathogenic	-0.377	Destabilizing	0.949	D	0.669	neutral	N	0.516220208	None	None	I
T/Q	0.2284	likely_benign	0.2275	benign	-1.207	Destabilizing	0.923	D	0.678	prob.neutral	None	None	None	None	I
T/R	0.2019	likely_benign	0.2063	benign	-0.922	Destabilizing	0.923	D	0.655	neutral	None	None	None	None	I
T/S	0.1226	likely_benign	0.1244	benign	-1.57	Destabilizing	0.034	N	0.267	neutral	D	0.529037804	None	None	I
T/V	0.1366	likely_benign	0.1384	benign	-0.377	Destabilizing	0.633	D	0.539	neutral	None	None	None	None	I
T/W	0.6061	likely_pathogenic	0.6129	pathogenic	-0.786	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	I
T/Y	0.2769	likely_benign	0.281	benign	-0.452	Destabilizing	0.987	D	0.74	deleterious	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.