TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31961	96106;96107;96108	chr2:178544348;178544347;178544346	chr2:179409075;179409074;179409073
N2AB	30320	91183;91184;91185	chr2:178544348;178544347;178544346	chr2:179409075;179409074;179409073
N2A	29393	88402;88403;88404	chr2:178544348;178544347;178544346	chr2:179409075;179409074;179409073
N2B	22896	68911;68912;68913	chr2:178544348;178544347;178544346	chr2:179409075;179409074;179409073
Novex-1	23021	69286;69287;69288	chr2:178544348;178544347;178544346	chr2:179409075;179409074;179409073
Novex-2	23088	69487;69488;69489	chr2:178544348;178544347;178544346	chr2:179409075;179409074;179409073
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: Fn3-121
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6185
• 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	rs1696035879	None	0.008	N	0.14	0.06	0.117506650769	gnomAD-4.0.0	1.59136E-06	None	None	None	None	I	None	5.65611E-05	0	None	0	0	None	0	0	0	0	0
T/I	rs1336039632	0.068	0.901	N	0.474	0.314	0.393927044628	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65673E-04

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	0.0665	likely_benign	0.0678	benign	-0.187	Destabilizing	0.008	N	0.14	neutral	N	0.451293804	None	None	I
T/C	0.2901	likely_benign	0.3246	benign	-0.263	Destabilizing	0.989	D	0.504	neutral	None	None	None	None	I
T/D	0.2758	likely_benign	0.2682	benign	0.044	Stabilizing	0.923	D	0.397	neutral	None	None	None	None	I
T/E	0.2046	likely_benign	0.199	benign	-0.044	Destabilizing	0.775	D	0.398	neutral	None	None	None	None	I
T/F	0.2561	likely_benign	0.2681	benign	-0.801	Destabilizing	0.961	D	0.577	neutral	None	None	None	None	I
T/G	0.1434	likely_benign	0.1506	benign	-0.271	Destabilizing	0.633	D	0.445	neutral	None	None	None	None	I
T/H	0.1871	likely_benign	0.1934	benign	-0.452	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	I
T/I	0.1561	likely_benign	0.1624	benign	-0.09	Destabilizing	0.901	D	0.474	neutral	N	0.47039964	None	None	I
T/K	0.1198	likely_benign	0.1188	benign	-0.277	Destabilizing	0.775	D	0.409	neutral	None	None	None	None	I
T/L	0.0939	likely_benign	0.0945	benign	-0.09	Destabilizing	0.633	D	0.42	neutral	None	None	None	None	I
T/M	0.1027	likely_benign	0.1031	benign	-0.093	Destabilizing	0.996	D	0.487	neutral	None	None	None	None	I
T/N	0.0989	likely_benign	0.0991	benign	-0.033	Destabilizing	0.901	D	0.378	neutral	N	0.466492543	None	None	I
T/P	0.0762	likely_benign	0.0746	benign	-0.096	Destabilizing	0.949	D	0.469	neutral	N	0.466783332	None	None	I
T/Q	0.1491	likely_benign	0.1539	benign	-0.252	Destabilizing	0.961	D	0.467	neutral	None	None	None	None	I
T/R	0.1163	likely_benign	0.1171	benign	0.03	Stabilizing	0.923	D	0.469	neutral	None	None	None	None	I
T/S	0.081	likely_benign	0.0831	benign	-0.199	Destabilizing	0.092	N	0.133	neutral	N	0.451813879	None	None	I
T/V	0.1172	likely_benign	0.1211	benign	-0.096	Destabilizing	0.633	D	0.402	neutral	None	None	None	None	I
T/W	0.5138	ambiguous	0.5318	ambiguous	-0.877	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	I
T/Y	0.2407	likely_benign	0.2557	benign	-0.56	Destabilizing	0.987	D	0.571	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.