TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5467	16624;16625;16626	chr2:178732662;178732661;178732660	chr2:179597389;179597388;179597387
N2AB	5150	15673;15674;15675	chr2:178732662;178732661;178732660	chr2:179597389;179597388;179597387
N2A	4223	12892;12893;12894	chr2:178732662;178732661;178732660	chr2:179597389;179597388;179597387
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-38
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2746
• 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
V/F	None	None	0.942	N	0.811	0.286	0.720981639776	gnomAD-4.0.0	1.59912E-06	None	None	None	None	N	None	5.69411E-05	0	None	0	0	None	0	0	0	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
V/A	0.1777	likely_benign	0.2139	benign	-1.905	Destabilizing	0.822	D	0.531	neutral	N	0.496825732	None	None	N
V/C	0.7995	likely_pathogenic	0.8315	pathogenic	-1.311	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
V/D	0.6614	likely_pathogenic	0.8255	pathogenic	-1.864	Destabilizing	0.99	D	0.817	deleterious	D	0.524851267	None	None	N
V/E	0.5704	likely_pathogenic	0.7336	pathogenic	-1.684	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
V/F	0.173	likely_benign	0.2486	benign	-1.133	Destabilizing	0.942	D	0.811	deleterious	N	0.479880118	None	None	N
V/G	0.3234	likely_benign	0.4148	ambiguous	-2.395	Highly Destabilizing	0.971	D	0.802	deleterious	N	0.497846242	None	None	N
V/H	0.7963	likely_pathogenic	0.8902	pathogenic	-1.844	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
V/I	0.0803	likely_benign	0.0835	benign	-0.566	Destabilizing	0.014	N	0.237	neutral	N	0.47208479	None	None	N
V/K	0.7061	likely_pathogenic	0.8384	pathogenic	-1.555	Destabilizing	0.978	D	0.806	deleterious	None	None	None	None	N
V/L	0.2058	likely_benign	0.2649	benign	-0.566	Destabilizing	0.247	N	0.477	neutral	N	0.496017656	None	None	N
V/M	0.187	likely_benign	0.2317	benign	-0.523	Destabilizing	0.956	D	0.731	prob.delet.	None	None	None	None	N
V/N	0.5568	ambiguous	0.7139	pathogenic	-1.71	Destabilizing	0.993	D	0.836	deleterious	None	None	None	None	N
V/P	0.8111	likely_pathogenic	0.9028	pathogenic	-0.983	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
V/Q	0.6107	likely_pathogenic	0.7468	pathogenic	-1.611	Destabilizing	0.993	D	0.825	deleterious	None	None	None	None	N
V/R	0.6252	likely_pathogenic	0.7745	pathogenic	-1.317	Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	N
V/S	0.3262	likely_benign	0.4353	ambiguous	-2.378	Highly Destabilizing	0.978	D	0.785	deleterious	None	None	None	None	N
V/T	0.2536	likely_benign	0.3278	benign	-2.047	Highly Destabilizing	0.86	D	0.675	neutral	None	None	None	None	N
V/W	0.8655	likely_pathogenic	0.9319	pathogenic	-1.471	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
V/Y	0.6334	likely_pathogenic	0.7605	pathogenic	-1.119	Destabilizing	0.978	D	0.809	deleterious	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.