TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1774	5545;5546;5547	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269
N2AB	1774	5545;5546;5547	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269
N2A	1774	5545;5546;5547	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269
N2B	1728	5407;5408;5409	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269
Novex-1	1728	5407;5408;5409	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269
Novex-2	1728	5407;5408;5409	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269
Novex-3	1774	5545;5546;5547	chr2:178776544;178776543;178776542	chr2:179641271;179641270;179641269

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-8
• Domain position: 72
• Structural Position: 153
• Q(SASA): 0.6039
• 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
I/V	rs758207512	-0.437	None	N	0.177	0.126	0.349870743963	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
I/A	0.558	ambiguous	0.5488	ambiguous	-1.293	Destabilizing	0.035	N	0.419	neutral	None	None	None	None	I
I/C	0.8299	likely_pathogenic	0.8238	pathogenic	-0.728	Destabilizing	0.824	D	0.583	neutral	None	None	None	None	I
I/D	0.8954	likely_pathogenic	0.9056	pathogenic	-1.0	Destabilizing	0.555	D	0.616	neutral	None	None	None	None	I
I/E	0.81	likely_pathogenic	0.8231	pathogenic	-1.07	Destabilizing	0.555	D	0.608	neutral	None	None	None	None	I
I/F	0.3488	ambiguous	0.3561	ambiguous	-1.28	Destabilizing	0.317	N	0.518	neutral	N	0.51273392	None	None	I
I/G	0.7982	likely_pathogenic	0.7968	pathogenic	-1.529	Destabilizing	0.262	N	0.583	neutral	None	None	None	None	I
I/H	0.7788	likely_pathogenic	0.7923	pathogenic	-0.829	Destabilizing	0.935	D	0.609	neutral	None	None	None	None	I
I/K	0.7448	likely_pathogenic	0.7683	pathogenic	-0.65	Destabilizing	0.555	D	0.608	neutral	None	None	None	None	I
I/L	0.1922	likely_benign	0.1928	benign	-0.754	Destabilizing	0.005	N	0.307	neutral	N	0.501101369	None	None	I
I/M	0.1604	likely_benign	0.1664	benign	-0.394	Destabilizing	0.317	N	0.559	neutral	N	0.507636492	None	None	I
I/N	0.4689	ambiguous	0.5047	ambiguous	-0.396	Destabilizing	0.741	D	0.62	neutral	N	0.505690121	None	None	I
I/P	0.9206	likely_pathogenic	0.9254	pathogenic	-0.902	Destabilizing	0.791	D	0.622	neutral	None	None	None	None	I
I/Q	0.6965	likely_pathogenic	0.7176	pathogenic	-0.712	Destabilizing	0.791	D	0.625	neutral	None	None	None	None	I
I/R	0.7004	likely_pathogenic	0.7153	pathogenic	-0.022	Destabilizing	0.555	D	0.619	neutral	None	None	None	None	I
I/S	0.5261	ambiguous	0.5336	ambiguous	-0.922	Destabilizing	0.117	N	0.581	neutral	N	0.496782521	None	None	I
I/T	0.3599	ambiguous	0.369	ambiguous	-0.886	Destabilizing	0.062	N	0.496	neutral	N	0.412275645	None	None	I
I/V	0.0596	likely_benign	0.0587	benign	-0.902	Destabilizing	None	N	0.177	neutral	N	0.45421318	None	None	I
I/W	0.9448	likely_pathogenic	0.9459	pathogenic	-1.296	Destabilizing	0.935	D	0.62	neutral	None	None	None	None	I
I/Y	0.7453	likely_pathogenic	0.7661	pathogenic	-1.025	Destabilizing	0.555	D	0.597	neutral	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.