TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25812	77659;77660;77661	chr2:178568698;178568697;178568696	chr2:179433425;179433424;179433423
N2AB	24171	72736;72737;72738	chr2:178568698;178568697;178568696	chr2:179433425;179433424;179433423
N2A	23244	69955;69956;69957	chr2:178568698;178568697;178568696	chr2:179433425;179433424;179433423
N2B	16747	50464;50465;50466	chr2:178568698;178568697;178568696	chr2:179433425;179433424;179433423
Novex-1	16872	50839;50840;50841	chr2:178568698;178568697;178568696	chr2:179433425;179433424;179433423
Novex-2	16939	51040;51041;51042	chr2:178568698;178568697;178568696	chr2:179433425;179433424;179433423
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-136
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.26
• Predicted PPI site: N

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/S	None	None	1.0	D	0.875	0.626	0.649944800967	gnomAD-4.0.0	1.59228E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85972E-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
G/A	0.4917	ambiguous	0.5031	ambiguous	-0.447	Destabilizing	1.0	D	0.803	deleterious	D	0.624290296	None	None	N
G/C	0.5028	ambiguous	0.5374	ambiguous	-0.874	Destabilizing	1.0	D	0.865	deleterious	D	0.662274218	None	None	N
G/D	0.4683	ambiguous	0.5182	ambiguous	-0.969	Destabilizing	1.0	D	0.897	deleterious	D	0.592958787	None	None	N
G/E	0.6011	likely_pathogenic	0.6414	pathogenic	-1.134	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/F	0.8795	likely_pathogenic	0.9021	pathogenic	-1.179	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/H	0.657	likely_pathogenic	0.691	pathogenic	-0.742	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/I	0.9031	likely_pathogenic	0.9186	pathogenic	-0.529	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/K	0.7149	likely_pathogenic	0.7466	pathogenic	-0.974	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/L	0.8151	likely_pathogenic	0.8347	pathogenic	-0.529	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
G/M	0.8589	likely_pathogenic	0.8734	pathogenic	-0.376	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/N	0.4389	ambiguous	0.4561	ambiguous	-0.595	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/P	0.9846	likely_pathogenic	0.9878	pathogenic	-0.468	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/Q	0.5868	likely_pathogenic	0.6127	pathogenic	-0.941	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/R	0.596	likely_pathogenic	0.6374	pathogenic	-0.463	Destabilizing	1.0	D	0.898	deleterious	D	0.645619084	None	None	N
G/S	0.2332	likely_benign	0.2392	benign	-0.719	Destabilizing	1.0	D	0.875	deleterious	D	0.601800686	None	None	N
G/T	0.5884	likely_pathogenic	0.617	pathogenic	-0.825	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/V	0.8372	likely_pathogenic	0.8607	pathogenic	-0.468	Destabilizing	1.0	D	0.865	deleterious	D	0.662072414	None	None	N
G/W	0.7634	likely_pathogenic	0.8026	pathogenic	-1.328	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
G/Y	0.7793	likely_pathogenic	0.8081	pathogenic	-0.986	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N

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.