TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27925	83998;83999;84000	chr2:178562359;178562358;178562357	chr2:179427086;179427085;179427084
N2AB	26284	79075;79076;79077	chr2:178562359;178562358;178562357	chr2:179427086;179427085;179427084
N2A	25357	76294;76295;76296	chr2:178562359;178562358;178562357	chr2:179427086;179427085;179427084
N2B	18860	56803;56804;56805	chr2:178562359;178562358;178562357	chr2:179427086;179427085;179427084
Novex-1	18985	57178;57179;57180	chr2:178562359;178562358;178562357	chr2:179427086;179427085;179427084
Novex-2	19052	57379;57380;57381	chr2:178562359;178562358;178562357	chr2:179427086;179427085;179427084
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: Fn3-91
• Domain position: 63
• Structural Position: 96
• Q(SASA): 0.5343
• 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/A	None	None	0.937	N	0.639	0.417	0.344710718752	gnomAD-4.0.0	1.59986E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44965E-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	0.1957	likely_benign	0.2146	benign	-0.273	Destabilizing	0.937	D	0.639	neutral	N	0.518411211	None	None	N
G/C	0.2955	likely_benign	0.3212	benign	-0.841	Destabilizing	1.0	D	0.753	deleterious	D	0.528072449	None	None	N
G/D	0.2687	likely_benign	0.3015	benign	-0.398	Destabilizing	0.188	N	0.506	neutral	N	0.513038484	None	None	N
G/E	0.3389	likely_benign	0.3881	ambiguous	-0.553	Destabilizing	0.995	D	0.758	deleterious	None	None	None	None	N
G/F	0.6568	likely_pathogenic	0.7021	pathogenic	-0.988	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/H	0.3961	ambiguous	0.4326	ambiguous	-0.509	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/I	0.5022	ambiguous	0.5682	pathogenic	-0.392	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/K	0.5138	ambiguous	0.5611	ambiguous	-0.728	Destabilizing	0.997	D	0.733	prob.delet.	None	None	None	None	N
G/L	0.5368	ambiguous	0.5734	pathogenic	-0.392	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
G/M	0.5707	likely_pathogenic	0.6101	pathogenic	-0.474	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
G/N	0.2296	likely_benign	0.2467	benign	-0.377	Destabilizing	0.995	D	0.765	deleterious	None	None	None	None	N
G/P	0.9302	likely_pathogenic	0.9374	pathogenic	-0.32	Destabilizing	0.997	D	0.763	deleterious	None	None	None	None	N
G/Q	0.3721	ambiguous	0.4125	ambiguous	-0.634	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
G/R	0.3622	ambiguous	0.4189	ambiguous	-0.321	Destabilizing	0.998	D	0.776	deleterious	N	0.492166654	None	None	N
G/S	0.1137	likely_benign	0.125	benign	-0.549	Destabilizing	0.981	D	0.769	deleterious	N	0.48718945	None	None	N
G/T	0.2324	likely_benign	0.2592	benign	-0.626	Destabilizing	0.997	D	0.734	prob.delet.	None	None	None	None	N
G/V	0.3711	ambiguous	0.4274	ambiguous	-0.32	Destabilizing	0.998	D	0.768	deleterious	D	0.52756547	None	None	N
G/W	0.5543	ambiguous	0.601	pathogenic	-1.148	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/Y	0.5194	ambiguous	0.5648	pathogenic	-0.788	Destabilizing	1.0	D	0.78	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.