TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8345	25258;25259;25260	chr2:178717973;178717972;178717971	chr2:179582700;179582699;179582698
N2AB	8028	24307;24308;24309	chr2:178717973;178717972;178717971	chr2:179582700;179582699;179582698
N2A	7101	21526;21527;21528	chr2:178717973;178717972;178717971	chr2:179582700;179582699;179582698
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-68
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1191
• Predicted PPI site: I

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	None	N	0.084	0.139	0.319114376414	gnomAD-4.0.0	6.37397E-06	None	None	None	None	I	None	0	2.28728E-05	None	0	0	None	0	0	8.59303E-06	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	0.1059	likely_benign	0.1261	benign	-1.099	Destabilizing	None	N	0.084	neutral	N	0.405188661	None	None	I
V/C	0.8231	likely_pathogenic	0.8641	pathogenic	-0.792	Destabilizing	0.002	N	0.355	neutral	None	None	None	None	I
V/D	0.4097	ambiguous	0.5082	ambiguous	-0.763	Destabilizing	0.001	N	0.365	neutral	N	0.430279106	None	None	I
V/E	0.3535	ambiguous	0.4347	ambiguous	-0.774	Destabilizing	0.001	N	0.281	neutral	None	None	None	None	I
V/F	0.2296	likely_benign	0.2677	benign	-0.811	Destabilizing	0.729	D	0.59	neutral	N	0.502915346	None	None	I
V/G	0.2792	likely_benign	0.3791	ambiguous	-1.382	Destabilizing	0.222	N	0.539	neutral	N	0.513993781	None	None	I
V/H	0.6741	likely_pathogenic	0.7595	pathogenic	-0.815	Destabilizing	0.94	D	0.595	neutral	None	None	None	None	I
V/I	0.0947	likely_benign	0.1038	benign	-0.442	Destabilizing	None	N	0.147	neutral	N	0.47897713	None	None	I
V/K	0.4194	ambiguous	0.4943	ambiguous	-0.945	Destabilizing	0.164	N	0.471	neutral	None	None	None	None	I
V/L	0.2932	likely_benign	0.3686	ambiguous	-0.442	Destabilizing	0.006	N	0.349	neutral	N	0.513473706	None	None	I
V/M	0.178	likely_benign	0.2101	benign	-0.462	Destabilizing	0.718	D	0.481	neutral	None	None	None	None	I
V/N	0.3621	ambiguous	0.4659	ambiguous	-0.773	Destabilizing	0.066	N	0.536	neutral	None	None	None	None	I
V/P	0.9106	likely_pathogenic	0.9574	pathogenic	-0.625	Destabilizing	0.126	N	0.581	neutral	None	None	None	None	I
V/Q	0.3898	ambiguous	0.4787	ambiguous	-0.921	Destabilizing	0.253	N	0.577	neutral	None	None	None	None	I
V/R	0.3801	ambiguous	0.4627	ambiguous	-0.442	Destabilizing	0.504	D	0.612	neutral	None	None	None	None	I
V/S	0.2074	likely_benign	0.2718	benign	-1.261	Destabilizing	0.009	N	0.302	neutral	None	None	None	None	I
V/T	0.1458	likely_benign	0.1703	benign	-1.16	Destabilizing	0.001	N	0.15	neutral	None	None	None	None	I
V/W	0.9021	likely_pathogenic	0.94	pathogenic	-0.978	Destabilizing	0.996	D	0.588	neutral	None	None	None	None	I
V/Y	0.6745	likely_pathogenic	0.7479	pathogenic	-0.673	Destabilizing	0.879	D	0.572	neutral	None	None	None	None	I

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.