TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32102	96529;96530;96531	chr2:178543840;178543839;178543838	chr2:179408567;179408566;179408565
N2AB	30461	91606;91607;91608	chr2:178543840;178543839;178543838	chr2:179408567;179408566;179408565
N2A	29534	88825;88826;88827	chr2:178543840;178543839;178543838	chr2:179408567;179408566;179408565
N2B	23037	69334;69335;69336	chr2:178543840;178543839;178543838	chr2:179408567;179408566;179408565
Novex-1	23162	69709;69710;69711	chr2:178543840;178543839;178543838	chr2:179408567;179408566;179408565
Novex-2	23229	69910;69911;69912	chr2:178543840;178543839;178543838	chr2:179408567;179408566;179408565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-153
• Domain position: 86
• Structural Position: 177
• Q(SASA): 0.3949
• 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/I	rs1297124100	-0.801	0.619	D	0.546	0.418	0.719968160526	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
V/I	rs1297124100	-0.801	0.619	D	0.546	0.418	0.719968160526	gnomAD-4.0.0	1.59218E-06	None	None	None	None	N	None	0	2.28697E-05	None	0	0	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	0.9617	likely_pathogenic	0.9473	pathogenic	-1.864	Destabilizing	0.992	D	0.663	neutral	D	0.656129009	None	None	N
V/C	0.9832	likely_pathogenic	0.9817	pathogenic	-1.316	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9983	pathogenic	-1.953	Destabilizing	1.0	D	0.753	deleterious	D	0.656734422	None	None	N
V/E	0.9976	likely_pathogenic	0.9956	pathogenic	-1.855	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
V/F	0.9826	likely_pathogenic	0.9735	pathogenic	-1.248	Destabilizing	0.999	D	0.759	deleterious	D	0.656129009	None	None	N
V/G	0.9745	likely_pathogenic	0.9629	pathogenic	-2.288	Highly Destabilizing	1.0	D	0.718	prob.delet.	D	0.656734422	None	None	N
V/H	0.9994	likely_pathogenic	0.9989	pathogenic	-1.904	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
V/I	0.1528	likely_benign	0.1444	benign	-0.741	Destabilizing	0.619	D	0.546	neutral	D	0.530438394	None	None	N
V/K	0.9984	likely_pathogenic	0.9973	pathogenic	-1.482	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
V/L	0.9493	likely_pathogenic	0.9324	pathogenic	-0.741	Destabilizing	0.962	D	0.689	prob.neutral	D	0.621840079	None	None	N
V/M	0.954	likely_pathogenic	0.9372	pathogenic	-0.645	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/N	0.9932	likely_pathogenic	0.9879	pathogenic	-1.466	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/P	0.9959	likely_pathogenic	0.9933	pathogenic	-1.084	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
V/Q	0.9981	likely_pathogenic	0.9967	pathogenic	-1.504	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/R	0.9966	likely_pathogenic	0.9945	pathogenic	-1.116	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/S	0.9842	likely_pathogenic	0.9754	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/T	0.9546	likely_pathogenic	0.9292	pathogenic	-1.858	Destabilizing	0.997	D	0.733	prob.delet.	None	None	None	None	N
V/W	0.9998	likely_pathogenic	0.9996	pathogenic	-1.596	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
V/Y	0.9976	likely_pathogenic	0.996	pathogenic	-1.264	Destabilizing	1.0	D	0.771	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.