TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34036	102331;102332;102333	chr2:178534509;178534508;178534507	chr2:179399236;179399235;179399234
N2AB	32395	97408;97409;97410	chr2:178534509;178534508;178534507	chr2:179399236;179399235;179399234
N2A	31468	94627;94628;94629	chr2:178534509;178534508;178534507	chr2:179399236;179399235;179399234
N2B	24971	75136;75137;75138	chr2:178534509;178534508;178534507	chr2:179399236;179399235;179399234
Novex-1	25096	75511;75512;75513	chr2:178534509;178534508;178534507	chr2:179399236;179399235;179399234
Novex-2	25163	75712;75713;75714	chr2:178534509;178534508;178534507	chr2:179399236;179399235;179399234
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Kinase-1
• Domain position: 224
• Q(SASA): 0.7231
• 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/K	None	None	None	N	None	0.203	0.262662153117	gnomAD-4.0.0	2.7369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69839E-06	1.1595E-05	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	0.2719	likely_benign	0.2339	benign	-0.201	Destabilizing	None	None	None	None	N	0.49228757	None	None	N
E/C	0.9349	likely_pathogenic	0.9345	pathogenic	-0.094	Destabilizing	None	None	None	None	None	None	None	None	N
E/D	0.2278	likely_benign	0.2194	benign	-0.234	Destabilizing	None	None	None	None	N	0.468122631	None	None	N
E/F	0.9061	likely_pathogenic	0.8793	pathogenic	-0.153	Destabilizing	None	None	None	None	None	None	None	None	N
E/G	0.2821	likely_benign	0.2641	benign	-0.362	Destabilizing	None	None	None	None	N	0.486516391	None	None	N
E/H	0.6922	likely_pathogenic	0.6733	pathogenic	0.278	Stabilizing	None	None	None	None	None	None	None	None	N
E/I	0.6458	likely_pathogenic	0.606	pathogenic	0.177	Stabilizing	None	None	None	None	None	None	None	None	N
E/K	0.2304	likely_benign	0.1883	benign	0.364	Stabilizing	None	None	None	None	N	0.488977906	None	None	N
E/L	0.6518	likely_pathogenic	0.6098	pathogenic	0.177	Stabilizing	None	None	None	None	None	None	None	None	N
E/M	0.7019	likely_pathogenic	0.6818	pathogenic	0.101	Stabilizing	None	None	None	None	None	None	None	None	N
E/N	0.4657	ambiguous	0.4666	ambiguous	0.103	Stabilizing	None	None	None	None	None	None	None	None	N
E/P	0.6007	likely_pathogenic	0.5457	ambiguous	0.071	Stabilizing	None	None	None	None	None	None	None	None	N
E/Q	0.2777	likely_benign	0.2615	benign	0.132	Stabilizing	None	None	None	None	N	0.496944028	None	None	N
E/R	0.3549	ambiguous	0.3013	benign	0.602	Stabilizing	None	None	None	None	None	None	None	None	N
E/S	0.3563	ambiguous	0.3395	benign	-0.058	Destabilizing	None	None	None	None	None	None	None	None	N
E/T	0.4059	ambiguous	0.3703	ambiguous	0.075	Stabilizing	None	None	None	None	None	None	None	None	N
E/V	0.4384	ambiguous	0.4021	ambiguous	0.071	Stabilizing	None	None	None	None	N	0.509622537	None	None	N
E/W	0.9563	likely_pathogenic	0.9481	pathogenic	-0.056	Destabilizing	None	None	None	None	None	None	None	None	N
E/Y	0.7974	likely_pathogenic	0.7689	pathogenic	0.078	Stabilizing	None	None	None	None	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.