TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26962	81109;81110;81111	chr2:178565248;178565247;178565246	chr2:179429975;179429974;179429973
N2AB	25321	76186;76187;76188	chr2:178565248;178565247;178565246	chr2:179429975;179429974;179429973
N2A	24394	73405;73406;73407	chr2:178565248;178565247;178565246	chr2:179429975;179429974;179429973
N2B	17897	53914;53915;53916	chr2:178565248;178565247;178565246	chr2:179429975;179429974;179429973
Novex-1	18022	54289;54290;54291	chr2:178565248;178565247;178565246	chr2:179429975;179429974;179429973
Novex-2	18089	54490;54491;54492	chr2:178565248;178565247;178565246	chr2:179429975;179429974;179429973
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-139
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.4302
• 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/A	None	None	0.201	D	0.435	0.169	0.251639045875	gnomAD-4.0.0	1.36855E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79905E-06	0	0
T/I	rs778900963	0.086	0.009	N	0.309	0.369	0.32306181527	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/I	rs778900963	0.086	0.009	N	0.309	0.369	0.32306181527	gnomAD-4.0.0	1.36855E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99533E-07	1.15947E-05	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	0.0771	likely_benign	0.0834	benign	-0.587	Destabilizing	0.201	N	0.435	neutral	D	0.531214105	None	None	I
T/C	0.3643	ambiguous	0.3895	ambiguous	-0.319	Destabilizing	0.992	D	0.587	neutral	None	None	None	None	I
T/D	0.39	ambiguous	0.4152	ambiguous	-0.168	Destabilizing	0.617	D	0.529	neutral	None	None	None	None	I
T/E	0.2223	likely_benign	0.24	benign	-0.217	Destabilizing	0.617	D	0.521	neutral	None	None	None	None	I
T/F	0.2524	likely_benign	0.2654	benign	-0.858	Destabilizing	0.85	D	0.649	neutral	None	None	None	None	I
T/G	0.2351	likely_benign	0.2585	benign	-0.784	Destabilizing	0.447	N	0.517	neutral	None	None	None	None	I
T/H	0.2429	likely_benign	0.2567	benign	-1.098	Destabilizing	0.992	D	0.639	neutral	None	None	None	None	I
T/I	0.1476	likely_benign	0.1496	benign	-0.171	Destabilizing	0.009	N	0.309	neutral	N	0.497612655	None	None	I
T/K	0.1384	likely_benign	0.1469	benign	-0.646	Destabilizing	0.549	D	0.526	neutral	D	0.53619585	None	None	I
T/L	0.1162	likely_benign	0.1187	benign	-0.171	Destabilizing	0.217	N	0.482	neutral	None	None	None	None	I
T/M	0.0893	likely_benign	0.0913	benign	0.135	Stabilizing	0.955	D	0.59	neutral	None	None	None	None	I
T/N	0.1549	likely_benign	0.1578	benign	-0.441	Destabilizing	0.85	D	0.469	neutral	None	None	None	None	I
T/P	0.4072	ambiguous	0.4438	ambiguous	-0.279	Destabilizing	0.009	N	0.295	neutral	D	0.5272378	None	None	I
T/Q	0.1654	likely_benign	0.1762	benign	-0.684	Destabilizing	0.92	D	0.605	neutral	None	None	None	None	I
T/R	0.1246	likely_benign	0.1302	benign	-0.332	Destabilizing	0.81	D	0.599	neutral	D	0.531926181	None	None	I
T/S	0.0934	likely_benign	0.0977	benign	-0.667	Destabilizing	0.016	N	0.167	neutral	N	0.45656163	None	None	I
T/V	0.1036	likely_benign	0.1052	benign	-0.279	Destabilizing	0.217	N	0.419	neutral	None	None	None	None	I
T/W	0.5909	likely_pathogenic	0.6262	pathogenic	-0.813	Destabilizing	0.992	D	0.683	prob.neutral	None	None	None	None	I
T/Y	0.3167	likely_benign	0.3318	benign	-0.575	Destabilizing	0.92	D	0.652	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.