TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27507	82744;82745;82746	chr2:178563613;178563612;178563611	chr2:179428340;179428339;179428338
N2AB	25866	77821;77822;77823	chr2:178563613;178563612;178563611	chr2:179428340;179428339;179428338
N2A	24939	75040;75041;75042	chr2:178563613;178563612;178563611	chr2:179428340;179428339;179428338
N2B	18442	55549;55550;55551	chr2:178563613;178563612;178563611	chr2:179428340;179428339;179428338
Novex-1	18567	55924;55925;55926	chr2:178563613;178563612;178563611	chr2:179428340;179428339;179428338
Novex-2	18634	56125;56126;56127	chr2:178563613;178563612;178563611	chr2:179428340;179428339;179428338
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-88
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1782
• 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
E/D	None	None	0.958	N	0.614	0.212	0.279370189704	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-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
E/A	0.8033	likely_pathogenic	0.8384	pathogenic	-1.59	Destabilizing	0.919	D	0.679	prob.neutral	D	0.534203926	None	None	N
E/C	0.9717	likely_pathogenic	0.9747	pathogenic	-0.862	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/D	0.8096	likely_pathogenic	0.7819	pathogenic	-1.714	Destabilizing	0.958	D	0.614	neutral	N	0.491336372	None	None	N
E/F	0.9639	likely_pathogenic	0.9692	pathogenic	-1.215	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/G	0.8226	likely_pathogenic	0.851	pathogenic	-1.994	Destabilizing	0.988	D	0.787	deleterious	D	0.535978352	None	None	N
E/H	0.9248	likely_pathogenic	0.9305	pathogenic	-1.195	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
E/I	0.9484	likely_pathogenic	0.9595	pathogenic	-0.427	Destabilizing	0.995	D	0.846	deleterious	None	None	None	None	N
E/K	0.8727	likely_pathogenic	0.906	pathogenic	-1.7	Destabilizing	0.919	D	0.654	neutral	N	0.521415589	None	None	N
E/L	0.8878	likely_pathogenic	0.9173	pathogenic	-0.427	Destabilizing	0.991	D	0.823	deleterious	None	None	None	None	N
E/M	0.9059	likely_pathogenic	0.9264	pathogenic	0.337	Stabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
E/N	0.9452	likely_pathogenic	0.9471	pathogenic	-1.925	Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
E/P	0.9993	likely_pathogenic	0.9993	pathogenic	-0.8	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
E/Q	0.3871	ambiguous	0.4449	ambiguous	-1.615	Destabilizing	0.414	N	0.335	neutral	N	0.510342108	None	None	N
E/R	0.8841	likely_pathogenic	0.9141	pathogenic	-1.503	Destabilizing	0.982	D	0.797	deleterious	None	None	None	None	N
E/S	0.8196	likely_pathogenic	0.837	pathogenic	-2.577	Highly Destabilizing	0.938	D	0.698	prob.neutral	None	None	None	None	N
E/T	0.9167	likely_pathogenic	0.9303	pathogenic	-2.199	Highly Destabilizing	0.991	D	0.79	deleterious	None	None	None	None	N
E/V	0.8621	likely_pathogenic	0.8898	pathogenic	-0.8	Destabilizing	0.988	D	0.817	deleterious	D	0.534964394	None	None	N
E/W	0.9798	likely_pathogenic	0.9799	pathogenic	-1.29	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/Y	0.9427	likely_pathogenic	0.9478	pathogenic	-1.05	Destabilizing	0.995	D	0.845	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.