TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34427	103504;103505;103506	chr2:178533336;178533335;178533334	chr2:179398063;179398062;179398061
N2AB	32786	98581;98582;98583	chr2:178533336;178533335;178533334	chr2:179398063;179398062;179398061
N2A	31859	95800;95801;95802	chr2:178533336;178533335;178533334	chr2:179398063;179398062;179398061
N2B	25362	76309;76310;76311	chr2:178533336;178533335;178533334	chr2:179398063;179398062;179398061
Novex-1	25487	76684;76685;76686	chr2:178533336;178533335;178533334	chr2:179398063;179398062;179398061
Novex-2	25554	76885;76886;76887	chr2:178533336;178533335;178533334	chr2:179398063;179398062;179398061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-162
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.4918
• 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
L/S	rs759702754	-0.993	0.781	N	0.757	0.427	0.552125808554	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/S	rs759702754	-0.993	0.781	N	0.757	0.427	0.552125808554	gnomAD-4.0.0	3.42117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.79656E-05	0
L/V	None	None	0.201	N	0.441	0.075	0.324436698001	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85762E-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
L/A	0.4566	ambiguous	0.423	ambiguous	-1.24	Destabilizing	0.399	N	0.58	neutral	None	None	None	None	N
L/C	0.5554	ambiguous	0.5866	pathogenic	-0.73	Destabilizing	0.982	D	0.721	prob.delet.	None	None	None	None	N
L/D	0.8442	likely_pathogenic	0.8275	pathogenic	-0.761	Destabilizing	0.935	D	0.828	deleterious	None	None	None	None	N
L/E	0.5256	ambiguous	0.4978	ambiguous	-0.836	Destabilizing	0.826	D	0.822	deleterious	None	None	None	None	N
L/F	0.1158	likely_benign	0.1144	benign	-1.128	Destabilizing	0.002	N	0.305	neutral	N	0.421966267	None	None	N
L/G	0.7727	likely_pathogenic	0.7375	pathogenic	-1.468	Destabilizing	0.826	D	0.799	deleterious	None	None	None	None	N
L/H	0.2462	likely_benign	0.2575	benign	-0.694	Destabilizing	0.982	D	0.806	deleterious	None	None	None	None	N
L/I	0.1923	likely_benign	0.1791	benign	-0.732	Destabilizing	0.25	N	0.426	neutral	None	None	None	None	N
L/K	0.2808	likely_benign	0.2569	benign	-0.744	Destabilizing	0.826	D	0.775	deleterious	None	None	None	None	N
L/M	0.1615	likely_benign	0.1515	benign	-0.456	Destabilizing	0.781	D	0.706	prob.neutral	N	0.466757194	None	None	N
L/N	0.5425	ambiguous	0.5081	ambiguous	-0.479	Destabilizing	0.935	D	0.834	deleterious	None	None	None	None	N
L/P	0.964	likely_pathogenic	0.9513	pathogenic	-0.868	Destabilizing	0.935	D	0.83	deleterious	None	None	None	None	N
L/Q	0.1959	likely_benign	0.1885	benign	-0.763	Destabilizing	0.935	D	0.797	deleterious	None	None	None	None	N
L/R	0.1902	likely_benign	0.1961	benign	-0.07	Destabilizing	0.826	D	0.794	deleterious	None	None	None	None	N
L/S	0.4323	ambiguous	0.4036	ambiguous	-0.998	Destabilizing	0.781	D	0.757	deleterious	N	0.435567496	None	None	N
L/T	0.4241	ambiguous	0.3912	ambiguous	-0.965	Destabilizing	0.826	D	0.699	prob.neutral	None	None	None	None	N
L/V	0.1796	likely_benign	0.1677	benign	-0.868	Destabilizing	0.201	N	0.441	neutral	N	0.450961023	None	None	N
L/W	0.3508	ambiguous	0.3717	ambiguous	-1.124	Destabilizing	0.931	D	0.789	deleterious	N	0.491061608	None	None	N
L/Y	0.3246	likely_benign	0.3352	benign	-0.895	Destabilizing	0.539	D	0.699	prob.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.