TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26477	79654;79655;79656	chr2:178566703;178566702;178566701	chr2:179431430;179431429;179431428
N2AB	24836	74731;74732;74733	chr2:178566703;178566702;178566701	chr2:179431430;179431429;179431428
N2A	23909	71950;71951;71952	chr2:178566703;178566702;178566701	chr2:179431430;179431429;179431428
N2B	17412	52459;52460;52461	chr2:178566703;178566702;178566701	chr2:179431430;179431429;179431428
Novex-1	17537	52834;52835;52836	chr2:178566703;178566702;178566701	chr2:179431430;179431429;179431428
Novex-2	17604	53035;53036;53037	chr2:178566703;178566702;178566701	chr2:179431430;179431429;179431428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-80
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.7386
• Predicted PPI site: N

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
V/I	rs1706005880	None	None	N	0.103	0.081	0.282179105231	gnomAD-4.0.0	4.10615E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39726E-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
V/A	0.0791	likely_benign	0.0772	benign	-0.828	Destabilizing	None	N	0.075	neutral	N	0.457851631	None	None	N
V/C	0.4325	ambiguous	0.3953	ambiguous	-0.71	Destabilizing	0.204	N	0.427	neutral	None	None	None	None	N
V/D	0.1903	likely_benign	0.1817	benign	-0.25	Destabilizing	0.026	N	0.529	neutral	N	0.473802518	None	None	N
V/E	0.1774	likely_benign	0.1752	benign	-0.264	Destabilizing	0.035	N	0.431	neutral	None	None	None	None	N
V/F	0.1389	likely_benign	0.1329	benign	-0.651	Destabilizing	0.046	N	0.568	neutral	N	0.477681753	None	None	N
V/G	0.1177	likely_benign	0.1148	benign	-1.053	Destabilizing	0.006	N	0.269	neutral	N	0.481613925	None	None	N
V/H	0.3156	likely_benign	0.3034	benign	-0.25	Destabilizing	0.439	N	0.431	neutral	None	None	None	None	N
V/I	0.0705	likely_benign	0.0668	benign	-0.332	Destabilizing	None	N	0.103	neutral	N	0.510107248	None	None	N
V/K	0.2066	likely_benign	0.2151	benign	-0.508	Destabilizing	0.035	N	0.429	neutral	None	None	None	None	N
V/L	0.091	likely_benign	0.0936	benign	-0.332	Destabilizing	None	N	0.14	neutral	N	0.494599078	None	None	N
V/M	0.0935	likely_benign	0.0889	benign	-0.543	Destabilizing	0.06	N	0.404	neutral	None	None	None	None	N
V/N	0.1298	likely_benign	0.1137	benign	-0.462	Destabilizing	0.035	N	0.585	neutral	None	None	None	None	N
V/P	0.1234	likely_benign	0.1113	benign	-0.464	Destabilizing	None	N	0.178	neutral	None	None	None	None	N
V/Q	0.1742	likely_benign	0.1757	benign	-0.569	Destabilizing	0.204	N	0.6	neutral	None	None	None	None	N
V/R	0.1945	likely_benign	0.2046	benign	-0.052	Destabilizing	0.035	N	0.601	neutral	None	None	None	None	N
V/S	0.0996	likely_benign	0.0949	benign	-0.95	Destabilizing	0.001	N	0.179	neutral	None	None	None	None	N
V/T	0.0954	likely_benign	0.0907	benign	-0.845	Destabilizing	0.007	N	0.184	neutral	None	None	None	None	N
V/W	0.6129	likely_pathogenic	0.5955	pathogenic	-0.752	Destabilizing	0.747	D	0.459	neutral	None	None	None	None	N
V/Y	0.352	ambiguous	0.3245	benign	-0.455	Destabilizing	0.204	N	0.565	neutral	None	None	None	None	N

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.