TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28042	84349;84350;84351	chr2:178562008;178562007;178562006	chr2:179426735;179426734;179426733
N2AB	26401	79426;79427;79428	chr2:178562008;178562007;178562006	chr2:179426735;179426734;179426733
N2A	25474	76645;76646;76647	chr2:178562008;178562007;178562006	chr2:179426735;179426734;179426733
N2B	18977	57154;57155;57156	chr2:178562008;178562007;178562006	chr2:179426735;179426734;179426733
Novex-1	19102	57529;57530;57531	chr2:178562008;178562007;178562006	chr2:179426735;179426734;179426733
Novex-2	19169	57730;57731;57732	chr2:178562008;178562007;178562006	chr2:179426735;179426734;179426733
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-142
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.3124
• 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
G/R	None	None	1.0	D	0.821	0.684	0.824278285417	gnomAD-4.0.0	1.5921E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43324E-05	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
G/A	0.576	likely_pathogenic	0.595	pathogenic	-0.227	Destabilizing	1.0	D	0.664	neutral	D	0.598514686	None	None	I
G/C	0.7622	likely_pathogenic	0.7696	pathogenic	-0.857	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
G/D	0.7935	likely_pathogenic	0.8254	pathogenic	-0.42	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
G/E	0.8637	likely_pathogenic	0.8773	pathogenic	-0.589	Destabilizing	1.0	D	0.817	deleterious	D	0.549793189	None	None	I
G/F	0.9647	likely_pathogenic	0.9669	pathogenic	-1.046	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/H	0.9413	likely_pathogenic	0.9498	pathogenic	-0.422	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
G/I	0.9519	likely_pathogenic	0.954	pathogenic	-0.47	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/K	0.9544	likely_pathogenic	0.9595	pathogenic	-0.546	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/L	0.956	likely_pathogenic	0.9571	pathogenic	-0.47	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/M	0.9645	likely_pathogenic	0.9675	pathogenic	-0.455	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/N	0.8612	likely_pathogenic	0.8722	pathogenic	-0.277	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
G/P	0.9974	likely_pathogenic	0.9978	pathogenic	-0.361	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/Q	0.8893	likely_pathogenic	0.9035	pathogenic	-0.567	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
G/R	0.895	likely_pathogenic	0.9037	pathogenic	-0.153	Destabilizing	1.0	D	0.821	deleterious	D	0.624254602	None	None	I
G/S	0.3879	ambiguous	0.4313	ambiguous	-0.413	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/T	0.784	likely_pathogenic	0.8027	pathogenic	-0.516	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/V	0.8966	likely_pathogenic	0.8993	pathogenic	-0.361	Destabilizing	1.0	D	0.803	deleterious	D	0.592589128	None	None	I
G/W	0.9623	likely_pathogenic	0.9666	pathogenic	-1.159	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/Y	0.949	likely_pathogenic	0.952	pathogenic	-0.814	Destabilizing	1.0	D	0.785	deleterious	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.