TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14456	43591;43592;43593	chr2:178632640;178632639;178632638	chr2:179497367;179497366;179497365
N2AB	12815	38668;38669;38670	chr2:178632640;178632639;178632638	chr2:179497367;179497366;179497365
N2A	11888	35887;35888;35889	chr2:178632640;178632639;178632638	chr2:179497367;179497366;179497365
N2B	5391	16396;16397;16398	chr2:178632640;178632639;178632638	chr2:179497367;179497366;179497365
Novex-1	5516	16771;16772;16773	chr2:178632640;178632639;178632638	chr2:179497367;179497366;179497365
Novex-2	5583	16972;16973;16974	chr2:178632640;178632639;178632638	chr2:179497367;179497366;179497365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-95
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.5275
• 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
I/R	None	None	0.002	N	0.295	0.216	0.526486031964	gnomAD-4.0.0	3.18364E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71912E-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
I/A	0.2959	likely_benign	0.3049	benign	-1.199	Destabilizing	0.129	N	0.33	neutral	None	None	None	None	N
I/C	0.6164	likely_pathogenic	0.5883	pathogenic	-0.702	Destabilizing	0.94	D	0.399	neutral	None	None	None	None	N
I/D	0.5607	ambiguous	0.5754	pathogenic	-0.686	Destabilizing	0.716	D	0.476	neutral	None	None	None	None	N
I/E	0.3305	likely_benign	0.3484	ambiguous	-0.728	Destabilizing	0.418	N	0.461	neutral	None	None	None	None	N
I/F	0.1224	likely_benign	0.1186	benign	-0.884	Destabilizing	0.418	N	0.35	neutral	None	None	None	None	N
I/G	0.5219	ambiguous	0.5327	ambiguous	-1.46	Destabilizing	0.418	N	0.432	neutral	None	None	None	None	N
I/H	0.2883	likely_benign	0.2806	benign	-0.646	Destabilizing	0.951	D	0.414	neutral	None	None	None	None	N
I/K	0.1687	likely_benign	0.1843	benign	-0.817	Destabilizing	0.213	N	0.443	neutral	N	0.461404282	None	None	N
I/L	0.0895	likely_benign	0.091	benign	-0.591	Destabilizing	None	N	0.093	neutral	N	0.422033189	None	None	N
I/M	0.0914	likely_benign	0.0905	benign	-0.475	Destabilizing	0.017	N	0.193	neutral	N	0.504602948	None	None	N
I/N	0.1688	likely_benign	0.1814	benign	-0.574	Destabilizing	0.716	D	0.473	neutral	None	None	None	None	N
I/P	0.8046	likely_pathogenic	0.8186	pathogenic	-0.76	Destabilizing	0.836	D	0.467	neutral	None	None	None	None	N
I/Q	0.2063	likely_benign	0.2131	benign	-0.787	Destabilizing	0.716	D	0.469	neutral	None	None	None	None	N
I/R	0.1196	likely_benign	0.1265	benign	-0.189	Destabilizing	0.002	N	0.295	neutral	N	0.48055884	None	None	N
I/S	0.2006	likely_benign	0.214	benign	-1.1	Destabilizing	0.264	N	0.411	neutral	None	None	None	None	N
I/T	0.1591	likely_benign	0.1697	benign	-1.031	Destabilizing	0.007	N	0.191	neutral	N	0.47861476	None	None	N
I/V	0.091	likely_benign	0.0945	benign	-0.76	Destabilizing	0.001	N	0.117	neutral	N	0.469751956	None	None	N
I/W	0.6044	likely_pathogenic	0.5636	ambiguous	-0.921	Destabilizing	0.983	D	0.431	neutral	None	None	None	None	N
I/Y	0.3993	ambiguous	0.372	ambiguous	-0.704	Destabilizing	0.836	D	0.449	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.