TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28998	87217;87218;87219	chr2:178558467;178558466;178558465	chr2:179423194;179423193;179423192
N2AB	27357	82294;82295;82296	chr2:178558467;178558466;178558465	chr2:179423194;179423193;179423192
N2A	26430	79513;79514;79515	chr2:178558467;178558466;178558465	chr2:179423194;179423193;179423192
N2B	19933	60022;60023;60024	chr2:178558467;178558466;178558465	chr2:179423194;179423193;179423192
Novex-1	20058	60397;60398;60399	chr2:178558467;178558466;178558465	chr2:179423194;179423193;179423192
Novex-2	20125	60598;60599;60600	chr2:178558467;178558466;178558465	chr2:179423194;179423193;179423192
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: Fn3-99
• Domain position: 57
• Structural Position: 89
• Q(SASA): 0.2201
• 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
T/A	None	None	0.775	N	0.4	0.373	0.233785782151	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85802E-06	0	0
T/I	rs1206763274	None	0.789	N	0.36	0.303	0.390531646278	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0822	likely_benign	0.0845	benign	-0.834	Destabilizing	0.775	D	0.4	neutral	N	0.475220353	None	None	N
T/C	0.284	likely_benign	0.2675	benign	-0.367	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
T/D	0.5787	likely_pathogenic	0.6277	pathogenic	-0.543	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
T/E	0.5151	ambiguous	0.5536	ambiguous	-0.386	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	N
T/F	0.3242	likely_benign	0.3764	ambiguous	-0.699	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
T/G	0.2003	likely_benign	0.2106	benign	-1.217	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
T/H	0.352	ambiguous	0.3935	ambiguous	-1.319	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
T/I	0.1674	likely_benign	0.1912	benign	0.147	Stabilizing	0.789	D	0.36	neutral	N	0.504285714	None	None	N
T/K	0.3512	ambiguous	0.3492	ambiguous	-0.203	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
T/L	0.0623	likely_benign	0.062	benign	0.147	Stabilizing	0.971	D	0.404	neutral	None	None	None	None	N
T/M	0.0848	likely_benign	0.0842	benign	0.111	Stabilizing	0.971	D	0.363	neutral	None	None	None	None	N
T/N	0.1243	likely_benign	0.138	benign	-0.727	Destabilizing	0.998	D	0.529	neutral	N	0.50536315	None	None	N
T/P	0.0748	likely_benign	0.0808	benign	-0.147	Destabilizing	0.998	D	0.604	neutral	N	0.496762309	None	None	N
T/Q	0.2689	likely_benign	0.2825	benign	-0.549	Destabilizing	0.998	D	0.618	neutral	None	None	None	None	N
T/R	0.2855	likely_benign	0.2857	benign	-0.352	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
T/S	0.105	likely_benign	0.1131	benign	-1.017	Destabilizing	0.944	D	0.413	neutral	N	0.498223747	None	None	N
T/V	0.1226	likely_benign	0.134	benign	-0.147	Destabilizing	0.959	D	0.399	neutral	None	None	None	None	N
T/W	0.7309	likely_pathogenic	0.7771	pathogenic	-0.821	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
T/Y	0.3965	ambiguous	0.4451	ambiguous	-0.424	Destabilizing	1.0	D	0.675	prob.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.