TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31919	95980;95981;95982	chr2:178544474;178544473;178544472	chr2:179409201;179409200;179409199
N2AB	30278	91057;91058;91059	chr2:178544474;178544473;178544472	chr2:179409201;179409200;179409199
N2A	29351	88276;88277;88278	chr2:178544474;178544473;178544472	chr2:179409201;179409200;179409199
N2B	22854	68785;68786;68787	chr2:178544474;178544473;178544472	chr2:179409201;179409200;179409199
Novex-1	22979	69160;69161;69162	chr2:178544474;178544473;178544472	chr2:179409201;179409200;179409199
Novex-2	23046	69361;69362;69363	chr2:178544474;178544473;178544472	chr2:179409201;179409200;179409199
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-121
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.578
• 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/M	rs1696086052	None	0.989	N	0.431	0.286	0.492475246742	gnomAD-4.0.0	1.60365E-06	None	None	None	None	N	None	5.68117E-05	0	None	0	0	None	0	0	0	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	0.114	likely_benign	0.1206	benign	-0.816	Destabilizing	0.625	D	0.377	neutral	N	0.502010626	None	None	N
V/C	0.6693	likely_pathogenic	0.7142	pathogenic	-0.748	Destabilizing	0.998	D	0.431	neutral	None	None	None	None	N
V/D	0.4611	ambiguous	0.4732	ambiguous	-0.427	Destabilizing	0.728	D	0.478	neutral	None	None	None	None	N
V/E	0.309	likely_benign	0.3191	benign	-0.528	Destabilizing	0.012	N	0.263	neutral	N	0.48373151	None	None	N
V/F	0.1942	likely_benign	0.1882	benign	-0.897	Destabilizing	0.991	D	0.448	neutral	None	None	None	None	N
V/G	0.2334	likely_benign	0.2269	benign	-0.984	Destabilizing	0.891	D	0.487	neutral	D	0.522809973	None	None	N
V/H	0.5476	ambiguous	0.5699	pathogenic	-0.414	Destabilizing	0.993	D	0.477	neutral	None	None	None	None	N
V/I	0.0681	likely_benign	0.068	benign	-0.516	Destabilizing	0.688	D	0.407	neutral	None	None	None	None	N
V/K	0.2804	likely_benign	0.2968	benign	-0.593	Destabilizing	0.728	D	0.484	neutral	None	None	None	None	N
V/L	0.1554	likely_benign	0.168	benign	-0.516	Destabilizing	0.625	D	0.443	neutral	N	0.450659086	None	None	N
V/M	0.1103	likely_benign	0.1126	benign	-0.423	Destabilizing	0.989	D	0.431	neutral	N	0.50270406	None	None	N
V/N	0.2863	likely_benign	0.305	benign	-0.355	Destabilizing	0.949	D	0.466	neutral	None	None	None	None	N
V/P	0.8561	likely_pathogenic	0.8387	pathogenic	-0.58	Destabilizing	0.974	D	0.466	neutral	None	None	None	None	N
V/Q	0.3102	likely_benign	0.3188	benign	-0.635	Destabilizing	0.904	D	0.472	neutral	None	None	None	None	N
V/R	0.2637	likely_benign	0.26	benign	-0.003	Destabilizing	0.949	D	0.501	neutral	None	None	None	None	N
V/S	0.1652	likely_benign	0.1734	benign	-0.793	Destabilizing	0.728	D	0.428	neutral	None	None	None	None	N
V/T	0.086	likely_benign	0.0904	benign	-0.794	Destabilizing	0.029	N	0.089	neutral	None	None	None	None	N
V/W	0.7794	likely_pathogenic	0.7887	pathogenic	-0.93	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
V/Y	0.5573	ambiguous	0.5708	pathogenic	-0.65	Destabilizing	0.991	D	0.445	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.