TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25432	76519;76520;76521	chr2:178569838;178569837;178569836	chr2:179434565;179434564;179434563
N2AB	23791	71596;71597;71598	chr2:178569838;178569837;178569836	chr2:179434565;179434564;179434563
N2A	22864	68815;68816;68817	chr2:178569838;178569837;178569836	chr2:179434565;179434564;179434563
N2B	16367	49324;49325;49326	chr2:178569838;178569837;178569836	chr2:179434565;179434564;179434563
Novex-1	16492	49699;49700;49701	chr2:178569838;178569837;178569836	chr2:179434565;179434564;179434563
Novex-2	16559	49900;49901;49902	chr2:178569838;178569837;178569836	chr2:179434565;179434564;179434563
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-73
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.259
• 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
D/G	rs760107858	-1.376	1.0	N	0.678	0.555	0.380052290102	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	1.65837E-04
D/G	rs760107858	-1.376	1.0	N	0.678	0.555	0.380052290102	gnomAD-4.0.0	3.18365E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	4.83559E-04	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
D/A	0.849	likely_pathogenic	0.8871	pathogenic	-0.548	Destabilizing	1.0	D	0.707	prob.neutral	N	0.481537002	None	None	N
D/C	0.9659	likely_pathogenic	0.9725	pathogenic	-0.297	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
D/E	0.8294	likely_pathogenic	0.8622	pathogenic	-0.74	Destabilizing	1.0	D	0.447	neutral	N	0.491056429	None	None	N
D/F	0.9807	likely_pathogenic	0.9856	pathogenic	-0.202	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
D/G	0.814	likely_pathogenic	0.8557	pathogenic	-0.915	Destabilizing	1.0	D	0.678	prob.neutral	N	0.511530995	None	None	N
D/H	0.8857	likely_pathogenic	0.9	pathogenic	-0.687	Destabilizing	1.0	D	0.645	neutral	N	0.501224646	None	None	N
D/I	0.9643	likely_pathogenic	0.974	pathogenic	0.427	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
D/K	0.9629	likely_pathogenic	0.9715	pathogenic	-0.632	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
D/L	0.9493	likely_pathogenic	0.9635	pathogenic	0.427	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/M	0.9835	likely_pathogenic	0.9879	pathogenic	0.909	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
D/N	0.2367	likely_benign	0.224	benign	-1.01	Destabilizing	1.0	D	0.673	neutral	N	0.47059877	None	None	N
D/P	0.9765	likely_pathogenic	0.9834	pathogenic	0.128	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
D/Q	0.9435	likely_pathogenic	0.9555	pathogenic	-0.831	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
D/R	0.9541	likely_pathogenic	0.9631	pathogenic	-0.534	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
D/S	0.4933	ambiguous	0.5259	ambiguous	-1.286	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/T	0.817	likely_pathogenic	0.8348	pathogenic	-0.984	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
D/V	0.9135	likely_pathogenic	0.9335	pathogenic	0.128	Stabilizing	1.0	D	0.691	prob.neutral	N	0.518821922	None	None	N
D/W	0.9951	likely_pathogenic	0.9964	pathogenic	-0.088	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
D/Y	0.856	likely_pathogenic	0.8946	pathogenic	0.002	Stabilizing	1.0	D	0.622	neutral	D	0.538029041	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.