TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32826	98701;98702;98703	chr2:178539589;178539588;178539587	chr2:179404316;179404315;179404314
N2AB	31185	93778;93779;93780	chr2:178539589;178539588;178539587	chr2:179404316;179404315;179404314
N2A	30258	90997;90998;90999	chr2:178539589;178539588;178539587	chr2:179404316;179404315;179404314
N2B	23761	71506;71507;71508	chr2:178539589;178539588;178539587	chr2:179404316;179404315;179404314
Novex-1	23886	71881;71882;71883	chr2:178539589;178539588;178539587	chr2:179404316;179404315;179404314
Novex-2	23953	72082;72083;72084	chr2:178539589;178539588;178539587	chr2:179404316;179404315;179404314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-127
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.1526
• 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
A/T	None	None	0.885	N	0.662	0.165	0.353548585375	gnomAD-4.0.0	1.09469E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.43912E-05	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
A/C	0.3904	ambiguous	0.3358	benign	-0.835	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
A/D	0.4796	ambiguous	0.4179	ambiguous	-0.877	Destabilizing	0.982	D	0.715	prob.delet.	N	0.50280006	None	None	I
A/E	0.4937	ambiguous	0.4355	ambiguous	-0.955	Destabilizing	0.953	D	0.709	prob.delet.	None	None	None	None	I
A/F	0.5318	ambiguous	0.4747	ambiguous	-1.164	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	I
A/G	0.2268	likely_benign	0.1773	benign	-1.065	Destabilizing	0.76	D	0.643	neutral	N	0.448922716	None	None	I
A/H	0.6572	likely_pathogenic	0.5956	pathogenic	-1.166	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
A/I	0.5566	ambiguous	0.4814	ambiguous	-0.492	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	I
A/K	0.7847	likely_pathogenic	0.7365	pathogenic	-1.007	Destabilizing	0.953	D	0.705	prob.neutral	None	None	None	None	I
A/L	0.3394	likely_benign	0.287	benign	-0.492	Destabilizing	0.953	D	0.698	prob.neutral	None	None	None	None	I
A/M	0.3455	ambiguous	0.2876	benign	-0.342	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	I
A/N	0.4353	ambiguous	0.3611	ambiguous	-0.645	Destabilizing	0.986	D	0.712	prob.delet.	None	None	None	None	I
A/P	0.9721	likely_pathogenic	0.9613	pathogenic	-0.577	Destabilizing	0.991	D	0.703	prob.neutral	N	0.475776557	None	None	I
A/Q	0.5466	ambiguous	0.4923	ambiguous	-0.873	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	I
A/R	0.7049	likely_pathogenic	0.6762	pathogenic	-0.607	Destabilizing	0.986	D	0.709	prob.delet.	None	None	None	None	I
A/S	0.0835	likely_benign	0.0703	benign	-0.991	Destabilizing	0.079	N	0.425	neutral	N	0.353284468	None	None	I
A/T	0.1193	likely_benign	0.0964	benign	-0.978	Destabilizing	0.885	D	0.662	neutral	N	0.483926298	None	None	I
A/V	0.2672	likely_benign	0.218	benign	-0.577	Destabilizing	0.939	D	0.721	prob.delet.	N	0.501357265	None	None	I
A/W	0.8638	likely_pathogenic	0.8251	pathogenic	-1.4	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
A/Y	0.667	likely_pathogenic	0.6049	pathogenic	-1.028	Destabilizing	0.998	D	0.71	prob.delet.	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.