TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19311	58156;58157;58158	chr2:178594563;178594562;178594561	chr2:179459290;179459289;179459288
N2AB	17670	53233;53234;53235	chr2:178594563;178594562;178594561	chr2:179459290;179459289;179459288
N2A	16743	50452;50453;50454	chr2:178594563;178594562;178594561	chr2:179459290;179459289;179459288
N2B	10246	30961;30962;30963	chr2:178594563;178594562;178594561	chr2:179459290;179459289;179459288
Novex-1	10371	31336;31337;31338	chr2:178594563;178594562;178594561	chr2:179459290;179459289;179459288
Novex-2	10438	31537;31538;31539	chr2:178594563;178594562;178594561	chr2:179459290;179459289;179459288
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: Fn3-28
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.228
• 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/H	None	None	0.999	N	0.69	0.363	0.391775403332	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86048E-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
D/A	0.9285	likely_pathogenic	0.8913	pathogenic	-0.818	Destabilizing	0.993	D	0.628	neutral	N	0.494045397	None	None	I
D/C	0.9885	likely_pathogenic	0.9814	pathogenic	-0.371	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
D/E	0.9333	likely_pathogenic	0.9119	pathogenic	-0.742	Destabilizing	0.977	D	0.413	neutral	N	0.495829369	None	None	I
D/F	0.9929	likely_pathogenic	0.9869	pathogenic	-0.557	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
D/G	0.9274	likely_pathogenic	0.8895	pathogenic	-1.185	Destabilizing	0.955	D	0.5	neutral	N	0.519760202	None	None	I
D/H	0.9616	likely_pathogenic	0.9303	pathogenic	-0.904	Destabilizing	0.999	D	0.69	prob.neutral	N	0.493489192	None	None	I
D/I	0.9844	likely_pathogenic	0.9728	pathogenic	0.166	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	I
D/K	0.9862	likely_pathogenic	0.977	pathogenic	-0.607	Destabilizing	0.995	D	0.588	neutral	None	None	None	None	I
D/L	0.9756	likely_pathogenic	0.9606	pathogenic	0.166	Stabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
D/M	0.9931	likely_pathogenic	0.9878	pathogenic	0.745	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
D/N	0.4156	ambiguous	0.2704	benign	-0.991	Destabilizing	0.117	N	0.193	neutral	N	0.508766027	None	None	I
D/P	0.9834	likely_pathogenic	0.9742	pathogenic	-0.138	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
D/Q	0.9804	likely_pathogenic	0.9687	pathogenic	-0.837	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	I
D/R	0.9849	likely_pathogenic	0.9758	pathogenic	-0.526	Destabilizing	0.995	D	0.722	prob.delet.	None	None	None	None	I
D/S	0.7149	likely_pathogenic	0.6034	pathogenic	-1.354	Destabilizing	0.966	D	0.491	neutral	None	None	None	None	I
D/T	0.8668	likely_pathogenic	0.7854	pathogenic	-1.039	Destabilizing	0.995	D	0.571	neutral	None	None	None	None	I
D/V	0.9605	likely_pathogenic	0.931	pathogenic	-0.138	Destabilizing	0.997	D	0.722	prob.delet.	N	0.504503103	None	None	I
D/W	0.9982	likely_pathogenic	0.9965	pathogenic	-0.416	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
D/Y	0.9477	likely_pathogenic	0.9024	pathogenic	-0.316	Destabilizing	1.0	D	0.709	prob.delet.	D	0.537864457	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.