TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32940	99043;99044;99045	chr2:178539117;178539116;178539115	chr2:179403844;179403843;179403842
N2AB	31299	94120;94121;94122	chr2:178539117;178539116;178539115	chr2:179403844;179403843;179403842
N2A	30372	91339;91340;91341	chr2:178539117;178539116;178539115	chr2:179403844;179403843;179403842
N2B	23875	71848;71849;71850	chr2:178539117;178539116;178539115	chr2:179403844;179403843;179403842
Novex-1	24000	72223;72224;72225	chr2:178539117;178539116;178539115	chr2:179403844;179403843;179403842
Novex-2	24067	72424;72425;72426	chr2:178539117;178539116;178539115	chr2:179403844;179403843;179403842
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-128
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.779
• 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
S/C	None	None	0.997	N	0.566	0.451	0.465294738428	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
S/A	0.0781	likely_benign	0.0763	benign	-0.208	Destabilizing	0.489	N	0.448	neutral	N	0.470997073	None	None	N
S/C	0.1718	likely_benign	0.1635	benign	-0.214	Destabilizing	0.997	D	0.566	neutral	N	0.475776557	None	None	N
S/D	0.4472	ambiguous	0.3984	ambiguous	-0.128	Destabilizing	0.86	D	0.403	neutral	None	None	None	None	N
S/E	0.5962	likely_pathogenic	0.5261	ambiguous	-0.245	Destabilizing	0.86	D	0.401	neutral	None	None	None	None	N
S/F	0.2995	likely_benign	0.2806	benign	-0.932	Destabilizing	0.942	D	0.573	neutral	N	0.459396	None	None	N
S/G	0.084	likely_benign	0.077	benign	-0.257	Destabilizing	0.86	D	0.409	neutral	None	None	None	None	N
S/H	0.4414	ambiguous	0.3899	ambiguous	-0.674	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	N
S/I	0.2572	likely_benign	0.2434	benign	-0.21	Destabilizing	0.915	D	0.483	neutral	None	None	None	None	N
S/K	0.719	likely_pathogenic	0.6166	pathogenic	-0.375	Destabilizing	0.86	D	0.409	neutral	None	None	None	None	N
S/L	0.1313	likely_benign	0.1164	benign	-0.21	Destabilizing	0.754	D	0.469	neutral	None	None	None	None	N
S/M	0.2345	likely_benign	0.1992	benign	0.026	Stabilizing	0.559	D	0.451	neutral	None	None	None	None	N
S/N	0.1434	likely_benign	0.122	benign	-0.069	Destabilizing	0.86	D	0.411	neutral	None	None	None	None	N
S/P	0.3961	ambiguous	0.4464	ambiguous	-0.185	Destabilizing	0.97	D	0.507	neutral	N	0.458857282	None	None	N
S/Q	0.5626	ambiguous	0.4753	ambiguous	-0.371	Destabilizing	0.978	D	0.455	neutral	None	None	None	None	N
S/R	0.6986	likely_pathogenic	0.6137	pathogenic	-0.09	Destabilizing	0.956	D	0.507	neutral	None	None	None	None	N
S/T	0.0762	likely_benign	0.068	benign	-0.189	Destabilizing	0.014	N	0.345	neutral	N	0.473805305	None	None	N
S/V	0.2216	likely_benign	0.205	benign	-0.185	Destabilizing	0.754	D	0.443	neutral	None	None	None	None	N
S/W	0.5529	ambiguous	0.5242	ambiguous	-0.982	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
S/Y	0.3066	likely_benign	0.2964	benign	-0.683	Destabilizing	0.99	D	0.591	neutral	N	0.520809818	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.