TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4874	14845;14846;14847	chr2:178735826;178735825;178735824	chr2:179600553;179600552;179600551
N2AB	4557	13894;13895;13896	chr2:178735826;178735825;178735824	chr2:179600553;179600552;179600551
N2A	3630	11113;11114;11115	chr2:178735826;178735825;178735824	chr2:179600553;179600552;179600551
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-31
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.1809
• 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/V	None	None	1.0	D	0.833	0.786	0.930366645497	gnomAD-4.0.0	6.84249E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99468E-07	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
G/A	0.6561	likely_pathogenic	0.7289	pathogenic	-0.372	Destabilizing	1.0	D	0.743	deleterious	D	0.730805163	None	None	I
G/C	0.9116	likely_pathogenic	0.9258	pathogenic	-0.964	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/D	0.9402	likely_pathogenic	0.9538	pathogenic	-0.733	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/E	0.9562	likely_pathogenic	0.9664	pathogenic	-0.902	Destabilizing	1.0	D	0.829	deleterious	D	0.740964939	None	None	I
G/F	0.9828	likely_pathogenic	0.9856	pathogenic	-1.121	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/H	0.9703	likely_pathogenic	0.9781	pathogenic	-0.543	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/I	0.9745	likely_pathogenic	0.9773	pathogenic	-0.563	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/K	0.977	likely_pathogenic	0.9812	pathogenic	-0.888	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
G/L	0.9665	likely_pathogenic	0.9731	pathogenic	-0.563	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/M	0.9831	likely_pathogenic	0.9865	pathogenic	-0.589	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/N	0.9577	likely_pathogenic	0.9687	pathogenic	-0.555	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/P	0.9974	likely_pathogenic	0.9971	pathogenic	-0.468	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/Q	0.9487	likely_pathogenic	0.9591	pathogenic	-0.864	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/R	0.9209	likely_pathogenic	0.9311	pathogenic	-0.39	Destabilizing	1.0	D	0.856	deleterious	D	0.749112808	None	None	I
G/S	0.5887	likely_pathogenic	0.6563	pathogenic	-0.674	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/T	0.9113	likely_pathogenic	0.9232	pathogenic	-0.78	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/V	0.949	likely_pathogenic	0.9565	pathogenic	-0.468	Destabilizing	1.0	D	0.833	deleterious	D	0.830391993	None	None	I
G/W	0.968	likely_pathogenic	0.9716	pathogenic	-1.242	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/Y	0.9754	likely_pathogenic	0.979	pathogenic	-0.919	Destabilizing	1.0	D	0.835	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.