TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29421	88486;88487;88488	chr2:178556893;178556892;178556891	chr2:179421620;179421619;179421618
N2AB	27780	83563;83564;83565	chr2:178556893;178556892;178556891	chr2:179421620;179421619;179421618
N2A	26853	80782;80783;80784	chr2:178556893;178556892;178556891	chr2:179421620;179421619;179421618
N2B	20356	61291;61292;61293	chr2:178556893;178556892;178556891	chr2:179421620;179421619;179421618
Novex-1	20481	61666;61667;61668	chr2:178556893;178556892;178556891	chr2:179421620;179421619;179421618
Novex-2	20548	61867;61868;61869	chr2:178556893;178556892;178556891	chr2:179421620;179421619;179421618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-102
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.3267
• Predicted PPI site: I

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
N/H	None	None	0.999	N	0.549	0.262	0.273938319068	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.1762	likely_benign	0.168	benign	-0.756	Destabilizing	0.971	D	0.581	neutral	None	None	None	None	I
N/C	0.2415	likely_benign	0.2352	benign	0.13	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
N/D	0.2167	likely_benign	0.1935	benign	0.06	Stabilizing	0.98	D	0.584	neutral	N	0.346878571	None	None	I
N/E	0.4061	ambiguous	0.3605	ambiguous	0.075	Stabilizing	0.985	D	0.584	neutral	None	None	None	None	I
N/F	0.4826	ambiguous	0.4151	ambiguous	-0.901	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	I
N/G	0.259	likely_benign	0.258	benign	-0.996	Destabilizing	0.985	D	0.477	neutral	None	None	None	None	I
N/H	0.1184	likely_benign	0.1129	benign	-0.855	Destabilizing	0.999	D	0.549	neutral	N	0.432073326	None	None	I
N/I	0.1647	likely_benign	0.1442	benign	-0.188	Destabilizing	0.989	D	0.644	neutral	N	0.41158341	None	None	I
N/K	0.3001	likely_benign	0.2689	benign	-0.086	Destabilizing	0.98	D	0.581	neutral	N	0.370158075	None	None	I
N/L	0.1634	likely_benign	0.1491	benign	-0.188	Destabilizing	0.171	N	0.517	neutral	None	None	None	None	I
N/M	0.2811	likely_benign	0.2601	benign	0.218	Stabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
N/P	0.2888	likely_benign	0.2811	benign	-0.35	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
N/Q	0.3026	likely_benign	0.292	benign	-0.618	Destabilizing	0.998	D	0.562	neutral	None	None	None	None	I
N/R	0.3643	ambiguous	0.3227	benign	-0.037	Destabilizing	0.998	D	0.565	neutral	None	None	None	None	I
N/S	0.0802	likely_benign	0.0804	benign	-0.524	Destabilizing	0.659	D	0.306	neutral	N	0.434150839	None	None	I
N/T	0.1367	likely_benign	0.1289	benign	-0.332	Destabilizing	0.961	D	0.523	neutral	N	0.413140848	None	None	I
N/V	0.1688	likely_benign	0.1534	benign	-0.35	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	I
N/W	0.7847	likely_pathogenic	0.741	pathogenic	-0.748	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/Y	0.1699	likely_benign	0.1454	benign	-0.539	Destabilizing	0.999	D	0.723	prob.delet.	N	0.478557764	None	None	I

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.