TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27487	82684;82685;82686	chr2:178563673;178563672;178563671	chr2:179428400;179428399;179428398
N2AB	25846	77761;77762;77763	chr2:178563673;178563672;178563671	chr2:179428400;179428399;179428398
N2A	24919	74980;74981;74982	chr2:178563673;178563672;178563671	chr2:179428400;179428399;179428398
N2B	18422	55489;55490;55491	chr2:178563673;178563672;178563671	chr2:179428400;179428399;179428398
Novex-1	18547	55864;55865;55866	chr2:178563673;178563672;178563671	chr2:179428400;179428399;179428398
Novex-2	18614	56065;56066;56067	chr2:178563673;178563672;178563671	chr2:179428400;179428399;179428398
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-88
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2343
• 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/A	rs779268775	-1.713	0.174	N	0.435	0.281	0.537262924806	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	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	0.4109	ambiguous	0.4238	ambiguous	-1.681	Destabilizing	0.174	N	0.435	neutral	N	0.506013724	None	None	N
V/C	0.9178	likely_pathogenic	0.9185	pathogenic	-1.285	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
V/D	0.8638	likely_pathogenic	0.8905	pathogenic	-1.668	Destabilizing	0.826	D	0.773	deleterious	None	None	None	None	N
V/E	0.7819	likely_pathogenic	0.8133	pathogenic	-1.649	Destabilizing	0.782	D	0.693	prob.neutral	N	0.494007219	None	None	N
V/F	0.4741	ambiguous	0.4673	ambiguous	-1.295	Destabilizing	0.826	D	0.638	neutral	None	None	None	None	N
V/G	0.6703	likely_pathogenic	0.6758	pathogenic	-2.025	Highly Destabilizing	0.782	D	0.744	deleterious	N	0.490678035	None	None	N
V/H	0.9142	likely_pathogenic	0.9173	pathogenic	-1.562	Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	N
V/I	0.0873	likely_benign	0.0855	benign	-0.819	Destabilizing	0.003	N	0.256	neutral	N	0.487601321	None	None	N
V/K	0.8856	likely_pathogenic	0.8977	pathogenic	-1.404	Destabilizing	0.826	D	0.691	prob.neutral	None	None	None	None	N
V/L	0.389	ambiguous	0.3663	ambiguous	-0.819	Destabilizing	0.068	N	0.404	neutral	N	0.507917878	None	None	N
V/M	0.2757	likely_benign	0.2696	benign	-0.673	Destabilizing	0.826	D	0.526	neutral	None	None	None	None	N
V/N	0.6839	likely_pathogenic	0.6955	pathogenic	-1.254	Destabilizing	0.826	D	0.793	deleterious	None	None	None	None	N
V/P	0.9738	likely_pathogenic	0.9695	pathogenic	-1.073	Destabilizing	0.906	D	0.722	prob.delet.	None	None	None	None	N
V/Q	0.8013	likely_pathogenic	0.8088	pathogenic	-1.417	Destabilizing	0.906	D	0.737	prob.delet.	None	None	None	None	N
V/R	0.8356	likely_pathogenic	0.8538	pathogenic	-0.899	Destabilizing	0.826	D	0.797	deleterious	None	None	None	None	N
V/S	0.529	ambiguous	0.5374	ambiguous	-1.811	Destabilizing	0.704	D	0.644	neutral	None	None	None	None	N
V/T	0.2223	likely_benign	0.2315	benign	-1.679	Destabilizing	0.01	N	0.408	neutral	None	None	None	None	N
V/W	0.9518	likely_pathogenic	0.9501	pathogenic	-1.501	Destabilizing	0.991	D	0.739	prob.delet.	None	None	None	None	N
V/Y	0.851	likely_pathogenic	0.8491	pathogenic	-1.211	Destabilizing	0.906	D	0.659	neutral	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.