TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5723	17392;17393;17394	chr2:178731708;178731707;178731706	chr2:179596435;179596434;179596433
N2AB	5406	16441;16442;16443	chr2:178731708;178731707;178731706	chr2:179596435;179596434;179596433
N2A	4479	13660;13661;13662	chr2:178731708;178731707;178731706	chr2:179596435;179596434;179596433
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-40
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.4901
• 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
R/T	rs2080550527	None	0.081	N	0.348	0.211	0.296329037015	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/T	rs2080550527	None	0.081	N	0.348	0.211	0.296329037015	gnomAD-4.0.0	6.57056E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47007E-05	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
R/A	0.1149	likely_benign	0.1095	benign	-0.295	Destabilizing	0.025	N	0.216	neutral	None	None	None	None	I
R/C	0.1556	likely_benign	0.1572	benign	-0.269	Destabilizing	0.958	D	0.446	neutral	None	None	None	None	I
R/D	0.247	likely_benign	0.2436	benign	0.062	Stabilizing	0.055	N	0.322	neutral	None	None	None	None	I
R/E	0.1387	likely_benign	0.1328	benign	0.153	Stabilizing	None	N	0.137	neutral	None	None	None	None	I
R/F	0.2933	likely_benign	0.2754	benign	-0.331	Destabilizing	0.497	N	0.511	neutral	None	None	None	None	I
R/G	0.0933	likely_benign	0.0956	benign	-0.553	Destabilizing	0.081	N	0.343	neutral	N	0.513702992	None	None	I
R/H	0.086	likely_benign	0.086	benign	-0.97	Destabilizing	0.667	D	0.428	neutral	None	None	None	None	I
R/I	0.1297	likely_benign	0.115	benign	0.371	Stabilizing	0.124	N	0.471	neutral	None	None	None	None	I
R/K	0.0675	likely_benign	0.0629	benign	-0.288	Destabilizing	None	N	0.134	neutral	N	0.450016873	None	None	I
R/L	0.1232	likely_benign	0.1121	benign	0.371	Stabilizing	None	N	0.235	neutral	None	None	None	None	I
R/M	0.1245	likely_benign	0.1106	benign	0.004	Stabilizing	0.427	N	0.458	neutral	N	0.484593594	None	None	I
R/N	0.2001	likely_benign	0.187	benign	0.15	Stabilizing	0.002	N	0.149	neutral	None	None	None	None	I
R/P	0.2424	likely_benign	0.2241	benign	0.171	Stabilizing	0.364	N	0.5	neutral	None	None	None	None	I
R/Q	0.0752	likely_benign	0.0741	benign	-0.014	Destabilizing	0.005	N	0.148	neutral	None	None	None	None	I
R/S	0.1504	likely_benign	0.1449	benign	-0.426	Destabilizing	0.042	N	0.283	neutral	N	0.412690636	None	None	I
R/T	0.0788	likely_benign	0.0736	benign	-0.174	Destabilizing	0.081	N	0.348	neutral	N	0.429102883	None	None	I
R/V	0.1444	likely_benign	0.1326	benign	0.171	Stabilizing	0.055	N	0.379	neutral	None	None	None	None	I
R/W	0.1436	likely_benign	0.1367	benign	-0.184	Destabilizing	0.946	D	0.455	neutral	N	0.473723239	None	None	I
R/Y	0.2276	likely_benign	0.2189	benign	0.175	Stabilizing	0.859	D	0.51	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.