TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7311	22156;22157;22158	chr2:178723076;178723075;178723074	chr2:179587803;179587802;179587801
N2AB	6994	21205;21206;21207	chr2:178723076;178723075;178723074	chr2:179587803;179587802;179587801
N2A	6067	18424;18425;18426	chr2:178723076;178723075;178723074	chr2:179587803;179587802;179587801
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-57
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2019
• 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
D/E	rs746715340	-0.436	0.948	N	0.472	0.364	0.306053231325	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/E	rs746715340	-0.436	0.948	N	0.472	0.364	0.306053231325	gnomAD-4.0.0	1.59181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85927E-06	0	0
D/N	rs1205648849	-0.783	0.989	N	0.597	0.402	0.366277470483	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66445E-04

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
D/A	0.3456	ambiguous	0.3678	ambiguous	-0.239	Destabilizing	0.978	D	0.645	neutral	N	0.49078606	None	None	I
D/C	0.8744	likely_pathogenic	0.9015	pathogenic	-0.09	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
D/E	0.4745	ambiguous	0.5153	ambiguous	-0.546	Destabilizing	0.948	D	0.472	neutral	N	0.498770609	None	None	I
D/F	0.9148	likely_pathogenic	0.9354	pathogenic	0.395	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
D/G	0.3496	ambiguous	0.3762	ambiguous	-0.643	Destabilizing	0.989	D	0.581	neutral	N	0.506572196	None	None	I
D/H	0.7385	likely_pathogenic	0.7557	pathogenic	0.11	Stabilizing	1.0	D	0.725	prob.delet.	D	0.540805697	None	None	I
D/I	0.8254	likely_pathogenic	0.8751	pathogenic	0.841	Stabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
D/K	0.8458	likely_pathogenic	0.8507	pathogenic	-0.222	Destabilizing	0.983	D	0.665	neutral	None	None	None	None	I
D/L	0.8318	likely_pathogenic	0.8634	pathogenic	0.841	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	I
D/M	0.9146	likely_pathogenic	0.937	pathogenic	1.16	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
D/N	0.2689	likely_benign	0.2921	benign	-0.783	Destabilizing	0.989	D	0.597	neutral	N	0.507697832	None	None	I
D/P	0.9875	likely_pathogenic	0.9898	pathogenic	0.508	Stabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
D/Q	0.7708	likely_pathogenic	0.7756	pathogenic	-0.578	Destabilizing	0.914	D	0.33	neutral	None	None	None	None	I
D/R	0.8722	likely_pathogenic	0.8664	pathogenic	-0.025	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	I
D/S	0.273	likely_benign	0.2837	benign	-1.071	Destabilizing	0.914	D	0.281	neutral	None	None	None	None	I
D/T	0.6082	likely_pathogenic	0.6392	pathogenic	-0.73	Destabilizing	0.983	D	0.673	neutral	None	None	None	None	I
D/V	0.5848	likely_pathogenic	0.6567	pathogenic	0.508	Stabilizing	0.998	D	0.786	deleterious	D	0.525071992	None	None	I
D/W	0.988	likely_pathogenic	0.9899	pathogenic	0.558	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
D/Y	0.6787	likely_pathogenic	0.7257	pathogenic	0.657	Stabilizing	0.999	D	0.799	deleterious	D	0.541059186	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.