TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16760	50503;50504;50505	chr2:178612133;178612132;178612131	chr2:179476860;179476859;179476858
N2AB	15119	45580;45581;45582	chr2:178612133;178612132;178612131	chr2:179476860;179476859;179476858
N2A	14192	42799;42800;42801	chr2:178612133;178612132;178612131	chr2:179476860;179476859;179476858
N2B	7695	23308;23309;23310	chr2:178612133;178612132;178612131	chr2:179476860;179476859;179476858
Novex-1	7820	23683;23684;23685	chr2:178612133;178612132;178612131	chr2:179476860;179476859;179476858
Novex-2	7887	23884;23885;23886	chr2:178612133;178612132;178612131	chr2:179476860;179476859;179476858
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-10
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2593
• 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
V/M	rs772739731	-0.375	0.968	D	0.579	0.419	0.617871938043	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
V/M	rs772739731	-0.375	0.968	D	0.579	0.419	0.617871938043	gnomAD-4.0.0	1.59599E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86474E-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
V/A	0.4553	ambiguous	0.4533	ambiguous	-1.311	Destabilizing	0.896	D	0.523	neutral	N	0.482396642	None	None	N
V/C	0.9263	likely_pathogenic	0.9185	pathogenic	-1.119	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
V/D	0.9568	likely_pathogenic	0.9641	pathogenic	-1.025	Destabilizing	0.988	D	0.757	deleterious	None	None	None	None	N
V/E	0.896	likely_pathogenic	0.9082	pathogenic	-0.97	Destabilizing	0.968	D	0.725	prob.delet.	D	0.631444545	None	None	N
V/F	0.5901	likely_pathogenic	0.5932	pathogenic	-0.844	Destabilizing	0.976	D	0.701	prob.neutral	None	None	None	None	N
V/G	0.795	likely_pathogenic	0.8103	pathogenic	-1.662	Destabilizing	0.968	D	0.724	prob.delet.	D	0.589449734	None	None	N
V/H	0.9689	likely_pathogenic	0.9738	pathogenic	-1.025	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
V/I	0.0863	likely_benign	0.08	benign	-0.431	Destabilizing	0.034	N	0.231	neutral	None	None	None	None	N
V/K	0.9043	likely_pathogenic	0.9136	pathogenic	-1.189	Destabilizing	0.976	D	0.726	prob.delet.	None	None	None	None	N
V/L	0.4406	ambiguous	0.4301	ambiguous	-0.431	Destabilizing	0.64	D	0.463	neutral	N	0.486607407	None	None	N
V/M	0.3531	ambiguous	0.3436	ambiguous	-0.535	Destabilizing	0.968	D	0.579	neutral	D	0.589751528	None	None	N
V/N	0.8933	likely_pathogenic	0.9065	pathogenic	-1.198	Destabilizing	0.988	D	0.768	deleterious	None	None	None	None	N
V/P	0.7961	likely_pathogenic	0.8075	pathogenic	-0.69	Destabilizing	0.076	N	0.412	neutral	None	None	None	None	N
V/Q	0.8945	likely_pathogenic	0.9049	pathogenic	-1.234	Destabilizing	0.988	D	0.747	deleterious	None	None	None	None	N
V/R	0.8949	likely_pathogenic	0.9066	pathogenic	-0.771	Destabilizing	0.988	D	0.775	deleterious	None	None	None	None	N
V/S	0.7578	likely_pathogenic	0.7733	pathogenic	-1.753	Destabilizing	0.976	D	0.689	prob.neutral	None	None	None	None	N
V/T	0.5121	ambiguous	0.5188	ambiguous	-1.562	Destabilizing	0.919	D	0.571	neutral	None	None	None	None	N
V/W	0.9844	likely_pathogenic	0.9852	pathogenic	-1.051	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
V/Y	0.9467	likely_pathogenic	0.9508	pathogenic	-0.732	Destabilizing	0.996	D	0.701	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.