TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8418	25477;25478;25479	chr2:178717622;178717621;178717620	chr2:179582349;179582348;179582347
N2AB	8101	24526;24527;24528	chr2:178717622;178717621;178717620	chr2:179582349;179582348;179582347
N2A	7174	21745;21746;21747	chr2:178717622;178717621;178717620	chr2:179582349;179582348;179582347
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-69
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.425
• 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	rs750071508	-1.128	0.995	N	0.495	0.214	0.342400092842	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	4.14E-05	8.51E-05	None	0	0	None	0	None	0	7.85E-06	0
Q/H	rs750071508	-1.128	0.995	N	0.495	0.214	0.342400092842	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
Q/H	rs750071508	-1.128	0.995	N	0.495	0.214	0.342400092842	gnomAD-4.0.0	3.42222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49816E-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	0.4635	ambiguous	0.4193	ambiguous	-0.72	Destabilizing	0.924	D	0.444	neutral	None	None	None	None	N
Q/C	0.8012	likely_pathogenic	0.7497	pathogenic	-0.264	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
Q/D	0.6466	likely_pathogenic	0.6091	pathogenic	-1.162	Destabilizing	0.012	N	0.337	neutral	None	None	None	None	N
Q/E	0.13	likely_benign	0.1289	benign	-1.004	Destabilizing	0.05	N	0.325	neutral	N	0.456481486	None	None	N
Q/F	0.8061	likely_pathogenic	0.7716	pathogenic	-0.288	Destabilizing	0.997	D	0.547	neutral	None	None	None	None	N
Q/G	0.5845	likely_pathogenic	0.5193	ambiguous	-1.128	Destabilizing	0.924	D	0.528	neutral	None	None	None	None	N
Q/H	0.2418	likely_benign	0.221	benign	-0.978	Destabilizing	0.995	D	0.495	neutral	N	0.503928716	None	None	N
Q/I	0.5619	ambiguous	0.5185	ambiguous	0.347	Stabilizing	0.976	D	0.579	neutral	None	None	None	None	N
Q/K	0.132	likely_benign	0.1166	benign	-0.462	Destabilizing	0.048	N	0.342	neutral	N	0.460772584	None	None	N
Q/L	0.2461	likely_benign	0.2185	benign	0.347	Stabilizing	0.899	D	0.556	neutral	N	0.45979115	None	None	N
Q/M	0.5208	ambiguous	0.4831	ambiguous	0.705	Stabilizing	0.996	D	0.498	neutral	None	None	None	None	N
Q/N	0.4299	ambiguous	0.4083	ambiguous	-1.155	Destabilizing	0.899	D	0.462	neutral	None	None	None	None	N
Q/P	0.9087	likely_pathogenic	0.8696	pathogenic	0.022	Stabilizing	0.976	D	0.521	neutral	N	0.509241541	None	None	N
Q/R	0.1292	likely_benign	0.1156	benign	-0.493	Destabilizing	0.744	D	0.483	neutral	N	0.458230925	None	None	N
Q/S	0.4404	ambiguous	0.4059	ambiguous	-1.265	Destabilizing	0.859	D	0.448	neutral	None	None	None	None	N
Q/T	0.3092	likely_benign	0.2819	benign	-0.907	Destabilizing	0.015	N	0.358	neutral	None	None	None	None	N
Q/V	0.4059	ambiguous	0.3672	ambiguous	0.022	Stabilizing	0.779	D	0.552	neutral	None	None	None	None	N
Q/W	0.6651	likely_pathogenic	0.5871	pathogenic	-0.208	Destabilizing	1.0	D	0.572	neutral	None	None	None	None	N
Q/Y	0.5616	ambiguous	0.5114	ambiguous	0.073	Stabilizing	0.997	D	0.548	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.