TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2816	8671;8672;8673	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980
N2AB	2816	8671;8672;8673	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980
N2A	2816	8671;8672;8673	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980
N2B	2770	8533;8534;8535	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980
Novex-1	2770	8533;8534;8535	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980
Novex-2	2770	8533;8534;8535	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980
Novex-3	2816	8671;8672;8673	chr2:178770255;178770254;178770253	chr2:179634982;179634981;179634980

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-18
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1225
• 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	None	None	0.012	N	0.443	0.131	0.295623431141	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.7461	likely_pathogenic	0.7819	pathogenic	-2.585	Highly Destabilizing	0.625	D	0.701	prob.neutral	N	0.449171149	None	None	N
V/C	0.912	likely_pathogenic	0.9238	pathogenic	-2.095	Highly Destabilizing	0.998	D	0.826	deleterious	None	None	None	None	N
V/D	0.9955	likely_pathogenic	0.9948	pathogenic	-3.496	Highly Destabilizing	0.989	D	0.871	deleterious	N	0.479340283	None	None	N
V/E	0.99	likely_pathogenic	0.989	pathogenic	-3.232	Highly Destabilizing	0.991	D	0.835	deleterious	None	None	None	None	N
V/F	0.6923	likely_pathogenic	0.7286	pathogenic	-1.431	Destabilizing	0.934	D	0.829	deleterious	N	0.461411232	None	None	N
V/G	0.8739	likely_pathogenic	0.8558	pathogenic	-3.112	Highly Destabilizing	0.966	D	0.844	deleterious	N	0.454024293	None	None	N
V/H	0.9977	likely_pathogenic	0.9975	pathogenic	-2.865	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
V/I	0.1127	likely_benign	0.1359	benign	-1.05	Destabilizing	0.012	N	0.443	neutral	N	0.445770683	None	None	N
V/K	0.9964	likely_pathogenic	0.9956	pathogenic	-2.233	Highly Destabilizing	0.974	D	0.837	deleterious	None	None	None	None	N
V/L	0.3268	likely_benign	0.3604	ambiguous	-1.05	Destabilizing	0.005	N	0.393	neutral	N	0.442256006	None	None	N
V/M	0.3943	ambiguous	0.435	ambiguous	-1.212	Destabilizing	0.172	N	0.501	neutral	None	None	None	None	N
V/N	0.9842	likely_pathogenic	0.9839	pathogenic	-2.729	Highly Destabilizing	0.991	D	0.87	deleterious	None	None	None	None	N
V/P	0.9986	likely_pathogenic	0.9983	pathogenic	-1.546	Destabilizing	0.991	D	0.855	deleterious	None	None	None	None	N
V/Q	0.9919	likely_pathogenic	0.9916	pathogenic	-2.48	Highly Destabilizing	0.974	D	0.854	deleterious	None	None	None	None	N
V/R	0.9942	likely_pathogenic	0.9932	pathogenic	-2.073	Highly Destabilizing	0.974	D	0.871	deleterious	None	None	None	None	N
V/S	0.9448	likely_pathogenic	0.9535	pathogenic	-3.243	Highly Destabilizing	0.915	D	0.822	deleterious	None	None	None	None	N
V/T	0.8157	likely_pathogenic	0.8292	pathogenic	-2.856	Highly Destabilizing	0.842	D	0.709	prob.delet.	None	None	None	None	N
V/W	0.9968	likely_pathogenic	0.9971	pathogenic	-2.043	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9785	likely_pathogenic	0.9804	pathogenic	-1.79	Destabilizing	0.974	D	0.826	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.