TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8067	24424;24425;24426	chr2:178719191;178719190;178719189	chr2:179583918;179583917;179583916
N2AB	7750	23473;23474;23475	chr2:178719191;178719190;178719189	chr2:179583918;179583917;179583916
N2A	6823	20692;20693;20694	chr2:178719191;178719190;178719189	chr2:179583918;179583917;179583916
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-65
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.6047
• 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
E/D	rs1319416113	None	0.014	D	0.285	0.241	0.149567049428	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1319416113	None	0.014	D	0.285	0.241	0.149567049428	gnomAD-4.0.0	6.57315E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4705E-05	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	0.1302	likely_benign	0.1479	benign	-0.694	Destabilizing	0.698	D	0.61	neutral	D	0.53183018	None	None	I
E/C	0.7945	likely_pathogenic	0.8501	pathogenic	-0.203	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	I
E/D	0.1652	likely_benign	0.1849	benign	-0.57	Destabilizing	0.014	N	0.285	neutral	D	0.533254332	None	None	I
E/F	0.6332	likely_pathogenic	0.7121	pathogenic	-0.293	Destabilizing	0.993	D	0.688	prob.neutral	None	None	None	None	I
E/G	0.1796	likely_benign	0.1934	benign	-0.961	Destabilizing	0.822	D	0.594	neutral	D	0.525680864	None	None	I
E/H	0.3326	likely_benign	0.3948	ambiguous	-0.208	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	I
E/I	0.2886	likely_benign	0.3604	ambiguous	0.004	Stabilizing	0.978	D	0.693	prob.neutral	None	None	None	None	I
E/K	0.0896	likely_benign	0.1044	benign	0.124	Stabilizing	0.822	D	0.546	neutral	D	0.532944901	None	None	I
E/L	0.3713	ambiguous	0.4584	ambiguous	0.004	Stabilizing	0.978	D	0.666	neutral	None	None	None	None	I
E/M	0.3559	ambiguous	0.4414	ambiguous	0.241	Stabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	I
E/N	0.2447	likely_benign	0.2917	benign	-0.396	Destabilizing	0.754	D	0.583	neutral	None	None	None	None	I
E/P	0.8795	likely_pathogenic	0.9005	pathogenic	-0.209	Destabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	I
E/Q	0.1055	likely_benign	0.1179	benign	-0.32	Destabilizing	0.942	D	0.617	neutral	N	0.486500535	None	None	I
E/R	0.1605	likely_benign	0.1903	benign	0.382	Stabilizing	0.978	D	0.635	neutral	None	None	None	None	I
E/S	0.1611	likely_benign	0.1764	benign	-0.578	Destabilizing	0.193	N	0.386	neutral	None	None	None	None	I
E/T	0.1424	likely_benign	0.1717	benign	-0.349	Destabilizing	0.754	D	0.656	neutral	None	None	None	None	I
E/V	0.1729	likely_benign	0.2101	benign	-0.209	Destabilizing	0.971	D	0.666	neutral	D	0.538622866	None	None	I
E/W	0.8583	likely_pathogenic	0.9032	pathogenic	-0.011	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	I
E/Y	0.509	ambiguous	0.5968	pathogenic	-0.014	Destabilizing	0.993	D	0.698	prob.neutral	None	None	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.