TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20023	60292;60293;60294	chr2:178591752;178591751;178591750	chr2:179456479;179456478;179456477
N2AB	18382	55369;55370;55371	chr2:178591752;178591751;178591750	chr2:179456479;179456478;179456477
N2A	17455	52588;52589;52590	chr2:178591752;178591751;178591750	chr2:179456479;179456478;179456477
N2B	10958	33097;33098;33099	chr2:178591752;178591751;178591750	chr2:179456479;179456478;179456477
Novex-1	11083	33472;33473;33474	chr2:178591752;178591751;178591750	chr2:179456479;179456478;179456477
Novex-2	11150	33673;33674;33675	chr2:178591752;178591751;178591750	chr2:179456479;179456478;179456477
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-33
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5029
• 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/E	rs2050254249	None	0.014	N	0.334	0.077	0.210429274316	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	2.7804E-05	None	0	0	0	0	0
D/V	None	None	0.942	N	0.715	0.441	0.391930172978	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.1414	likely_benign	0.1409	benign	-0.29	Destabilizing	0.698	D	0.535	neutral	N	0.465340537	None	None	N
D/C	0.5674	likely_pathogenic	0.6081	pathogenic	-0.194	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
D/E	0.1046	likely_benign	0.0996	benign	-0.235	Destabilizing	0.014	N	0.334	neutral	N	0.419624103	None	None	N
D/F	0.5734	likely_pathogenic	0.5909	pathogenic	-0.194	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
D/G	0.1349	likely_benign	0.1408	benign	-0.471	Destabilizing	0.822	D	0.507	neutral	N	0.467263335	None	None	N
D/H	0.2283	likely_benign	0.2429	benign	0.161	Stabilizing	0.992	D	0.521	neutral	N	0.483715654	None	None	N
D/I	0.3013	likely_benign	0.3145	benign	0.136	Stabilizing	0.978	D	0.715	prob.delet.	None	None	None	None	N
D/K	0.2351	likely_benign	0.2497	benign	0.117	Stabilizing	0.754	D	0.493	neutral	None	None	None	None	N
D/L	0.3251	likely_benign	0.3385	benign	0.136	Stabilizing	0.956	D	0.714	prob.delet.	None	None	None	None	N
D/M	0.5154	ambiguous	0.5209	ambiguous	0.107	Stabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
D/N	0.0877	likely_benign	0.0882	benign	-0.106	Destabilizing	0.126	N	0.372	neutral	N	0.476922968	None	None	N
D/P	0.5804	likely_pathogenic	0.5969	pathogenic	0.015	Stabilizing	0.978	D	0.517	neutral	None	None	None	None	N
D/Q	0.2167	likely_benign	0.2232	benign	-0.072	Destabilizing	0.915	D	0.492	neutral	None	None	None	None	N
D/R	0.3009	likely_benign	0.3299	benign	0.406	Stabilizing	0.956	D	0.645	neutral	None	None	None	None	N
D/S	0.1205	likely_benign	0.1207	benign	-0.252	Destabilizing	0.754	D	0.463	neutral	None	None	None	None	N
D/T	0.176	likely_benign	0.1791	benign	-0.112	Destabilizing	0.956	D	0.492	neutral	None	None	None	None	N
D/V	0.1723	likely_benign	0.181	benign	0.015	Stabilizing	0.942	D	0.715	prob.delet.	N	0.475096171	None	None	N
D/W	0.8252	likely_pathogenic	0.8512	pathogenic	-0.066	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
D/Y	0.2259	likely_benign	0.2504	benign	0.034	Stabilizing	0.997	D	0.697	prob.neutral	N	0.476790516	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.