TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28082	84469;84470;84471	chr2:178561888;178561887;178561886	chr2:179426615;179426614;179426613
N2AB	26441	79546;79547;79548	chr2:178561888;178561887;178561886	chr2:179426615;179426614;179426613
N2A	25514	76765;76766;76767	chr2:178561888;178561887;178561886	chr2:179426615;179426614;179426613
N2B	19017	57274;57275;57276	chr2:178561888;178561887;178561886	chr2:179426615;179426614;179426613
Novex-1	19142	57649;57650;57651	chr2:178561888;178561887;178561886	chr2:179426615;179426614;179426613
Novex-2	19209	57850;57851;57852	chr2:178561888;178561887;178561886	chr2:179426615;179426614;179426613
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-92
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2955
• 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
D/N	None	None	0.884	N	0.256	0.416	0.292062946507	gnomAD-4.0.0	6.84315E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99509E-07	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
D/A	0.475	ambiguous	0.4414	ambiguous	-0.653	Destabilizing	0.999	D	0.615	neutral	N	0.491905803	None	None	I
D/C	0.8684	likely_pathogenic	0.8571	pathogenic	-0.31	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	I
D/E	0.4892	ambiguous	0.4317	ambiguous	-0.784	Destabilizing	0.996	D	0.469	neutral	N	0.488093914	None	None	I
D/F	0.9019	likely_pathogenic	0.8833	pathogenic	-0.388	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
D/G	0.4643	ambiguous	0.468	ambiguous	-1.019	Destabilizing	0.996	D	0.605	neutral	D	0.53243318	None	None	I
D/H	0.6402	likely_pathogenic	0.6295	pathogenic	-0.806	Destabilizing	1.0	D	0.676	prob.neutral	N	0.511922615	None	None	I
D/I	0.7543	likely_pathogenic	0.708	pathogenic	0.321	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
D/K	0.7636	likely_pathogenic	0.7324	pathogenic	-0.615	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	I
D/L	0.707	likely_pathogenic	0.6607	pathogenic	0.321	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
D/M	0.8695	likely_pathogenic	0.846	pathogenic	0.852	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	I
D/N	0.144	likely_benign	0.1398	benign	-1.0	Destabilizing	0.884	D	0.256	neutral	N	0.479815482	None	None	I
D/P	0.9134	likely_pathogenic	0.8905	pathogenic	0.021	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
D/Q	0.7185	likely_pathogenic	0.6759	pathogenic	-0.834	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
D/R	0.7607	likely_pathogenic	0.7399	pathogenic	-0.528	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
D/S	0.2187	likely_benign	0.2112	benign	-1.306	Destabilizing	0.997	D	0.61	neutral	None	None	None	None	I
D/T	0.2904	likely_benign	0.2825	benign	-1.001	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
D/V	0.547	ambiguous	0.5007	ambiguous	0.021	Stabilizing	1.0	D	0.661	neutral	N	0.519809427	None	None	I
D/W	0.9792	likely_pathogenic	0.9759	pathogenic	-0.278	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
D/Y	0.5912	likely_pathogenic	0.566	pathogenic	-0.17	Destabilizing	1.0	D	0.647	neutral	D	0.550537435	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.