TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25260	76003;76004;76005	chr2:178570354;178570353;178570352	chr2:179435081;179435080;179435079
N2AB	23619	71080;71081;71082	chr2:178570354;178570353;178570352	chr2:179435081;179435080;179435079
N2A	22692	68299;68300;68301	chr2:178570354;178570353;178570352	chr2:179435081;179435080;179435079
N2B	16195	48808;48809;48810	chr2:178570354;178570353;178570352	chr2:179435081;179435080;179435079
Novex-1	16320	49183;49184;49185	chr2:178570354;178570353;178570352	chr2:179435081;179435080;179435079
Novex-2	16387	49384;49385;49386	chr2:178570354;178570353;178570352	chr2:179435081;179435080;179435079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-71
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7305
• 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
Q/H	rs1707726034	None	0.99	N	0.564	0.312	0.214338557667	gnomAD-4.0.0	8.21322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89547E-06	0	1.65728E-05
Q/R	None	None	0.904	N	0.523	0.275	0.201204373187	gnomAD-4.0.0	1.36887E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79919E-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
Q/A	0.166	likely_benign	0.2053	benign	-0.27	Destabilizing	0.86	D	0.547	neutral	None	None	None	None	N
Q/C	0.5735	likely_pathogenic	0.6719	pathogenic	0.217	Stabilizing	0.998	D	0.599	neutral	None	None	None	None	N
Q/D	0.3771	ambiguous	0.4226	ambiguous	-0.037	Destabilizing	0.974	D	0.509	neutral	None	None	None	None	N
Q/E	0.096	likely_benign	0.1012	benign	-0.057	Destabilizing	0.795	D	0.455	neutral	N	0.425512713	None	None	N
Q/F	0.6803	likely_pathogenic	0.7498	pathogenic	-0.396	Destabilizing	0.956	D	0.575	neutral	None	None	None	None	N
Q/G	0.2428	likely_benign	0.2763	benign	-0.484	Destabilizing	0.926	D	0.481	neutral	None	None	None	None	N
Q/H	0.2184	likely_benign	0.2464	benign	-0.426	Destabilizing	0.99	D	0.564	neutral	N	0.483040864	None	None	N
Q/I	0.3407	ambiguous	0.4235	ambiguous	0.209	Stabilizing	0.915	D	0.485	neutral	None	None	None	None	N
Q/K	0.0827	likely_benign	0.0865	benign	-0.018	Destabilizing	0.904	D	0.521	neutral	N	0.402502567	None	None	N
Q/L	0.1308	likely_benign	0.1651	benign	0.209	Stabilizing	0.014	N	0.284	neutral	N	0.502320058	None	None	N
Q/M	0.2908	likely_benign	0.3608	ambiguous	0.517	Stabilizing	0.956	D	0.567	neutral	None	None	None	None	N
Q/N	0.2533	likely_benign	0.288	benign	-0.323	Destabilizing	0.993	D	0.529	neutral	None	None	None	None	N
Q/P	0.0936	likely_benign	0.1126	benign	0.079	Stabilizing	0.99	D	0.576	neutral	N	0.436921785	None	None	N
Q/R	0.1051	likely_benign	0.1091	benign	0.119	Stabilizing	0.904	D	0.523	neutral	N	0.437788576	None	None	N
Q/S	0.1994	likely_benign	0.236	benign	-0.325	Destabilizing	0.926	D	0.497	neutral	None	None	None	None	N
Q/T	0.1528	likely_benign	0.1891	benign	-0.185	Destabilizing	0.86	D	0.529	neutral	None	None	None	None	N
Q/V	0.2	likely_benign	0.2668	benign	0.079	Stabilizing	0.754	D	0.494	neutral	None	None	None	None	N
Q/W	0.6371	likely_pathogenic	0.6795	pathogenic	-0.358	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
Q/Y	0.4963	ambiguous	0.5518	ambiguous	-0.118	Destabilizing	0.978	D	0.575	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.