TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30299	91120;91121;91122	chr2:178552005;178552004;178552003	chr2:179416732;179416731;179416730
N2AB	28658	86197;86198;86199	chr2:178552005;178552004;178552003	chr2:179416732;179416731;179416730
N2A	27731	83416;83417;83418	chr2:178552005;178552004;178552003	chr2:179416732;179416731;179416730
N2B	21234	63925;63926;63927	chr2:178552005;178552004;178552003	chr2:179416732;179416731;179416730
Novex-1	21359	64300;64301;64302	chr2:178552005;178552004;178552003	chr2:179416732;179416731;179416730
Novex-2	21426	64501;64502;64503	chr2:178552005;178552004;178552003	chr2:179416732;179416731;179416730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-108
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0976
• 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/L	rs774161568	-0.737	0.76	N	0.526	0.537	0.540288329166	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	0	None	0	2.05212E-04	None	0	None	0	0	0
V/L	rs774161568	-0.737	0.76	N	0.526	0.537	0.540288329166	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	3.861E-04	None	0	0	0	0	0
V/L	rs774161568	-0.737	0.76	N	0.526	0.537	0.540288329166	gnomAD-4.0.0	6.4142E-06	None	None	None	None	N	None	0	0	None	0	1.21324E-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	0.9098	likely_pathogenic	0.9013	pathogenic	-2.644	Highly Destabilizing	0.939	D	0.619	neutral	D	0.572394122	None	None	N
V/C	0.9696	likely_pathogenic	0.9706	pathogenic	-2.079	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
V/D	0.9988	likely_pathogenic	0.9986	pathogenic	-3.651	Highly Destabilizing	0.998	D	0.905	deleterious	None	None	None	None	N
V/E	0.9954	likely_pathogenic	0.9945	pathogenic	-3.339	Highly Destabilizing	0.997	D	0.889	deleterious	D	0.636216441	None	None	N
V/F	0.9226	likely_pathogenic	0.9173	pathogenic	-1.543	Destabilizing	0.986	D	0.824	deleterious	None	None	None	None	N
V/G	0.952	likely_pathogenic	0.9461	pathogenic	-3.217	Highly Destabilizing	0.997	D	0.907	deleterious	D	0.636216441	None	None	N
V/H	0.999	likely_pathogenic	0.9989	pathogenic	-3.046	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/I	0.0874	likely_benign	0.0944	benign	-0.958	Destabilizing	0.06	N	0.297	neutral	None	None	None	None	N
V/K	0.9968	likely_pathogenic	0.9964	pathogenic	-2.299	Highly Destabilizing	0.993	D	0.892	deleterious	None	None	None	None	N
V/L	0.6783	likely_pathogenic	0.6772	pathogenic	-0.958	Destabilizing	0.76	D	0.526	neutral	N	0.519950553	None	None	N
V/M	0.8129	likely_pathogenic	0.8037	pathogenic	-1.229	Destabilizing	0.982	D	0.707	prob.neutral	D	0.549935	None	None	N
V/N	0.9959	likely_pathogenic	0.9955	pathogenic	-2.988	Highly Destabilizing	0.998	D	0.919	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.9962	pathogenic	-1.505	Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
V/Q	0.9952	likely_pathogenic	0.9945	pathogenic	-2.645	Highly Destabilizing	0.998	D	0.913	deleterious	None	None	None	None	N
V/R	0.9936	likely_pathogenic	0.9929	pathogenic	-2.291	Highly Destabilizing	0.998	D	0.924	deleterious	None	None	None	None	N
V/S	0.9815	likely_pathogenic	0.9793	pathogenic	-3.448	Highly Destabilizing	0.993	D	0.888	deleterious	None	None	None	None	N
V/T	0.9545	likely_pathogenic	0.9508	pathogenic	-2.991	Highly Destabilizing	0.953	D	0.701	prob.neutral	None	None	None	None	N
V/W	0.999	likely_pathogenic	0.9989	pathogenic	-2.096	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
V/Y	0.9943	likely_pathogenic	0.9932	pathogenic	-1.846	Destabilizing	0.998	D	0.827	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.