TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27166	81721;81722;81723	chr2:178564636;178564635;178564634	chr2:179429363;179429362;179429361
N2AB	25525	76798;76799;76800	chr2:178564636;178564635;178564634	chr2:179429363;179429362;179429361
N2A	24598	74017;74018;74019	chr2:178564636;178564635;178564634	chr2:179429363;179429362;179429361
N2B	18101	54526;54527;54528	chr2:178564636;178564635;178564634	chr2:179429363;179429362;179429361
Novex-1	18226	54901;54902;54903	chr2:178564636;178564635;178564634	chr2:179429363;179429362;179429361
Novex-2	18293	55102;55103;55104	chr2:178564636;178564635;178564634	chr2:179429363;179429362;179429361
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-85
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3342
• 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/I	None	None	0.546	N	0.505	0.121	0.27132560031	gnomAD-4.0.0	1.36863E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99522E-07	1.15942E-05	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	0.2066	likely_benign	0.1793	benign	-1.304	Destabilizing	0.004	N	0.222	neutral	N	0.51564914	None	None	I
V/C	0.7095	likely_pathogenic	0.6271	pathogenic	-0.846	Destabilizing	0.011	N	0.522	neutral	None	None	None	None	I
V/D	0.71	likely_pathogenic	0.633	pathogenic	-1.039	Destabilizing	0.004	N	0.598	neutral	N	0.513334058	None	None	I
V/E	0.5631	ambiguous	0.5313	ambiguous	-1.06	Destabilizing	0.444	N	0.646	neutral	None	None	None	None	I
V/F	0.2352	likely_benign	0.1855	benign	-1.014	Destabilizing	0.895	D	0.619	neutral	N	0.466085185	None	None	I
V/G	0.3999	ambiguous	0.3569	ambiguous	-1.596	Destabilizing	0.376	N	0.727	deleterious	N	0.513334058	None	None	I
V/H	0.6937	likely_pathogenic	0.6341	pathogenic	-1.032	Destabilizing	0.992	D	0.802	deleterious	None	None	None	None	I
V/I	0.0783	likely_benign	0.0733	benign	-0.614	Destabilizing	0.546	D	0.505	neutral	N	0.494484434	None	None	I
V/K	0.5675	likely_pathogenic	0.5407	ambiguous	-1.091	Destabilizing	0.848	D	0.597	neutral	None	None	None	None	I
V/L	0.2008	likely_benign	0.1705	benign	-0.614	Destabilizing	0.199	N	0.479	neutral	N	0.512723478	None	None	I
V/M	0.1813	likely_benign	0.1585	benign	-0.468	Destabilizing	0.972	D	0.549	neutral	None	None	None	None	I
V/N	0.4714	ambiguous	0.4094	ambiguous	-0.848	Destabilizing	0.737	D	0.779	deleterious	None	None	None	None	I
V/P	0.5019	ambiguous	0.4495	ambiguous	-0.808	Destabilizing	0.919	D	0.684	prob.delet.	None	None	None	None	I
V/Q	0.4805	ambiguous	0.4536	ambiguous	-1.042	Destabilizing	0.919	D	0.731	deleterious	None	None	None	None	I
V/R	0.4701	ambiguous	0.4364	ambiguous	-0.512	Destabilizing	0.919	D	0.787	deleterious	None	None	None	None	I
V/S	0.2936	likely_benign	0.2465	benign	-1.354	Destabilizing	0.444	N	0.669	prob.neutral	None	None	None	None	I
V/T	0.1575	likely_benign	0.1462	benign	-1.266	Destabilizing	0.615	D	0.415	neutral	None	None	None	None	I
V/W	0.8501	likely_pathogenic	0.7859	pathogenic	-1.162	Destabilizing	0.992	D	0.795	deleterious	None	None	None	None	I
V/Y	0.6126	likely_pathogenic	0.5458	ambiguous	-0.885	Destabilizing	0.972	D	0.637	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.