TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25800	77623;77624;77625	chr2:178568734;178568733;178568732	chr2:179433461;179433460;179433459
N2AB	24159	72700;72701;72702	chr2:178568734;178568733;178568732	chr2:179433461;179433460;179433459
N2A	23232	69919;69920;69921	chr2:178568734;178568733;178568732	chr2:179433461;179433460;179433459
N2B	16735	50428;50429;50430	chr2:178568734;178568733;178568732	chr2:179433461;179433460;179433459
Novex-1	16860	50803;50804;50805	chr2:178568734;178568733;178568732	chr2:179433461;179433460;179433459
Novex-2	16927	51004;51005;51006	chr2:178568734;178568733;178568732	chr2:179433461;179433460;179433459
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-136
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2567
• 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
V/A	None	None	0.994	N	0.54	0.408	0.55767489547	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	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
V/A	0.3733	ambiguous	0.3891	ambiguous	-2.062	Highly Destabilizing	0.994	D	0.54	neutral	N	0.508350314	None	None	N
V/C	0.7654	likely_pathogenic	0.7714	pathogenic	-1.736	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/D	0.9786	likely_pathogenic	0.9809	pathogenic	-2.795	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/E	0.9542	likely_pathogenic	0.9579	pathogenic	-2.64	Highly Destabilizing	0.999	D	0.803	deleterious	N	0.496922599	None	None	N
V/F	0.4017	ambiguous	0.4145	ambiguous	-1.231	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/G	0.6413	likely_pathogenic	0.6504	pathogenic	-2.531	Highly Destabilizing	0.999	D	0.813	deleterious	N	0.507680924	None	None	N
V/H	0.9765	likely_pathogenic	0.9799	pathogenic	-2.254	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/I	0.0822	likely_benign	0.08	benign	-0.779	Destabilizing	0.543	D	0.333	neutral	N	0.466252975	None	None	N
V/K	0.9683	likely_pathogenic	0.9735	pathogenic	-1.798	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/L	0.3015	likely_benign	0.2923	benign	-0.779	Destabilizing	0.948	D	0.462	neutral	N	0.472216155	None	None	N
V/M	0.2765	likely_benign	0.2731	benign	-0.913	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
V/N	0.9336	likely_pathogenic	0.9396	pathogenic	-1.97	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/P	0.9487	likely_pathogenic	0.9547	pathogenic	-1.179	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/Q	0.9464	likely_pathogenic	0.9538	pathogenic	-1.921	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/R	0.9481	likely_pathogenic	0.9564	pathogenic	-1.509	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/S	0.7139	likely_pathogenic	0.7233	pathogenic	-2.51	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/T	0.5059	ambiguous	0.5252	ambiguous	-2.233	Highly Destabilizing	0.996	D	0.625	neutral	None	None	None	None	N
V/W	0.9668	likely_pathogenic	0.9696	pathogenic	-1.704	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/Y	0.888	likely_pathogenic	0.8968	pathogenic	-1.365	Destabilizing	1.0	D	0.835	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.