TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6707	20344;20345;20346	chr2:178727246;178727245;178727244	chr2:179591973;179591972;179591971
N2AB	6390	19393;19394;19395	chr2:178727246;178727245;178727244	chr2:179591973;179591972;179591971
N2A	5463	16612;16613;16614	chr2:178727246;178727245;178727244	chr2:179591973;179591972;179591971
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-51
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.3667
• 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
E/K	rs2079497465	None	0.14	N	0.198	0.292	0.30212335484	gnomAD-4.0.0	1.59256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02755E-05

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
E/A	0.1328	likely_benign	0.1392	benign	-0.517	Destabilizing	0.868	D	0.395	neutral	N	0.491581813	None	None	N
E/C	0.8509	likely_pathogenic	0.8437	pathogenic	-0.454	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/D	0.2881	likely_benign	0.3018	benign	-0.661	Destabilizing	0.632	D	0.393	neutral	N	0.485541426	None	None	N
E/F	0.7364	likely_pathogenic	0.758	pathogenic	0.132	Stabilizing	0.991	D	0.597	neutral	None	None	None	None	N
E/G	0.2312	likely_benign	0.2498	benign	-0.821	Destabilizing	0.064	N	0.248	neutral	D	0.536081207	None	None	N
E/H	0.464	ambiguous	0.4922	ambiguous	0.356	Stabilizing	0.999	D	0.446	neutral	None	None	None	None	N
E/I	0.2655	likely_benign	0.2675	benign	0.292	Stabilizing	0.19	N	0.367	neutral	None	None	None	None	N
E/K	0.1004	likely_benign	0.1147	benign	-0.106	Destabilizing	0.14	N	0.198	neutral	N	0.484135847	None	None	N
E/L	0.2959	likely_benign	0.3019	benign	0.292	Stabilizing	0.791	D	0.464	neutral	None	None	None	None	N
E/M	0.3654	ambiguous	0.3766	ambiguous	0.299	Stabilizing	0.973	D	0.572	neutral	None	None	None	None	N
E/N	0.3834	ambiguous	0.4207	ambiguous	-0.753	Destabilizing	0.961	D	0.4	neutral	None	None	None	None	N
E/P	0.307	likely_benign	0.3221	benign	0.043	Stabilizing	0.96	D	0.494	neutral	None	None	None	None	N
E/Q	0.1037	likely_benign	0.1085	benign	-0.622	Destabilizing	0.968	D	0.435	neutral	N	0.497911689	None	None	N
E/R	0.1859	likely_benign	0.2044	benign	0.336	Stabilizing	0.966	D	0.4	neutral	None	None	None	None	N
E/S	0.2254	likely_benign	0.2455	benign	-0.942	Destabilizing	0.897	D	0.363	neutral	None	None	None	None	N
E/T	0.2365	likely_benign	0.2568	benign	-0.68	Destabilizing	0.961	D	0.444	neutral	None	None	None	None	N
E/V	0.1706	likely_benign	0.1719	benign	0.043	Stabilizing	0.669	D	0.443	neutral	N	0.496052038	None	None	N
E/W	0.9233	likely_pathogenic	0.9342	pathogenic	0.413	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/Y	0.6357	likely_pathogenic	0.6619	pathogenic	0.401	Stabilizing	0.999	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.