TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17028	51307;51308;51309	chr2:178611047;178611046;178611045	chr2:179475774;179475773;179475772
N2AB	15387	46384;46385;46386	chr2:178611047;178611046;178611045	chr2:179475774;179475773;179475772
N2A	14460	43603;43604;43605	chr2:178611047;178611046;178611045	chr2:179475774;179475773;179475772
N2B	7963	24112;24113;24114	chr2:178611047;178611046;178611045	chr2:179475774;179475773;179475772
Novex-1	8088	24487;24488;24489	chr2:178611047;178611046;178611045	chr2:179475774;179475773;179475772
Novex-2	8155	24688;24689;24690	chr2:178611047;178611046;178611045	chr2:179475774;179475773;179475772
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-111
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.1872
• 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
T/I	rs1403894865	-0.13	0.013	N	0.459	0.291	0.32053947749	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	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
T/A	0.1216	likely_benign	0.1178	benign	-1.03	Destabilizing	0.429	N	0.627	neutral	D	0.55891321	None	None	N
T/C	0.4729	ambiguous	0.4973	ambiguous	-0.777	Destabilizing	0.995	D	0.744	deleterious	None	None	None	None	N
T/D	0.6347	likely_pathogenic	0.6533	pathogenic	-1.438	Destabilizing	0.945	D	0.762	deleterious	None	None	None	None	N
T/E	0.4844	ambiguous	0.4978	ambiguous	-1.299	Destabilizing	0.945	D	0.731	prob.delet.	None	None	None	None	N
T/F	0.3534	ambiguous	0.3854	ambiguous	-0.788	Destabilizing	0.894	D	0.8	deleterious	None	None	None	None	N
T/G	0.4259	ambiguous	0.4173	ambiguous	-1.41	Destabilizing	0.945	D	0.739	prob.delet.	None	None	None	None	N
T/H	0.2821	likely_benign	0.2925	benign	-1.665	Destabilizing	0.995	D	0.788	deleterious	None	None	None	None	N
T/I	0.1987	likely_benign	0.2138	benign	-0.056	Destabilizing	0.013	N	0.459	neutral	N	0.514260049	None	None	N
T/K	0.2372	likely_benign	0.239	benign	-0.721	Destabilizing	0.928	D	0.749	deleterious	N	0.506260971	None	None	N
T/L	0.1583	likely_benign	0.1651	benign	-0.056	Destabilizing	0.146	N	0.651	neutral	None	None	None	None	N
T/M	0.1162	likely_benign	0.1162	benign	0.111	Stabilizing	0.894	D	0.763	deleterious	None	None	None	None	N
T/N	0.1942	likely_benign	0.2011	benign	-1.232	Destabilizing	0.981	D	0.696	prob.neutral	None	None	None	None	N
T/P	0.837	likely_pathogenic	0.826	pathogenic	-0.348	Destabilizing	0.975	D	0.761	deleterious	D	0.689090076	None	None	N
T/Q	0.283	likely_benign	0.2798	benign	-1.148	Destabilizing	0.981	D	0.768	deleterious	None	None	None	None	N
T/R	0.2254	likely_benign	0.2242	benign	-0.788	Destabilizing	0.928	D	0.767	deleterious	N	0.510323634	None	None	N
T/S	0.1528	likely_benign	0.1502	benign	-1.406	Destabilizing	0.787	D	0.619	neutral	D	0.532847594	None	None	N
T/V	0.1744	likely_benign	0.184	benign	-0.348	Destabilizing	0.031	N	0.49	neutral	None	None	None	None	N
T/W	0.7911	likely_pathogenic	0.8142	pathogenic	-0.91	Destabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
T/Y	0.4381	ambiguous	0.4727	ambiguous	-0.566	Destabilizing	0.945	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.