TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2966	9121;9122;9123	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410
N2AB	2966	9121;9122;9123	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410
N2A	2966	9121;9122;9123	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410
N2B	2920	8983;8984;8985	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410
Novex-1	2920	8983;8984;8985	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410
Novex-2	2920	8983;8984;8985	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410
Novex-3	2966	9121;9122;9123	chr2:178769685;178769684;178769683	chr2:179634412;179634411;179634410

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-19
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.089
• 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	0.997	D	0.527	0.552	0.763078722514	gnomAD-4.0.0	1.20062E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66435E-05

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	0.8878	likely_pathogenic	0.9174	pathogenic	-1.424	Destabilizing	0.999	D	0.619	neutral	D	0.770099756	None	None	N
V/C	0.9794	likely_pathogenic	0.9875	pathogenic	-2.059	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9987	pathogenic	-3.203	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.768369075	None	None	N
V/E	0.9931	likely_pathogenic	0.9944	pathogenic	-3.137	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/F	0.9738	likely_pathogenic	0.9791	pathogenic	-1.042	Destabilizing	1.0	D	0.801	deleterious	D	0.768555823	None	None	N
V/G	0.9615	likely_pathogenic	0.9713	pathogenic	-1.732	Destabilizing	1.0	D	0.815	deleterious	D	0.768369075	None	None	N
V/H	0.9984	likely_pathogenic	0.9989	pathogenic	-1.181	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/I	0.165	likely_benign	0.1747	benign	-0.636	Destabilizing	0.997	D	0.527	neutral	D	0.598303146	None	None	N
V/K	0.9934	likely_pathogenic	0.9951	pathogenic	-1.413	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/L	0.8925	likely_pathogenic	0.9212	pathogenic	-0.636	Destabilizing	0.997	D	0.592	neutral	D	0.627265702	None	None	N
V/M	0.8603	likely_pathogenic	0.8807	pathogenic	-1.04	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
V/N	0.99	likely_pathogenic	0.9927	pathogenic	-1.751	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/P	0.9944	likely_pathogenic	0.9953	pathogenic	-0.872	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/Q	0.9933	likely_pathogenic	0.9947	pathogenic	-1.911	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/R	0.9904	likely_pathogenic	0.9922	pathogenic	-0.991	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/S	0.962	likely_pathogenic	0.973	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/T	0.8781	likely_pathogenic	0.9185	pathogenic	-1.89	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.359	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/Y	0.9978	likely_pathogenic	0.9984	pathogenic	-0.998	Destabilizing	1.0	D	0.811	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.