TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31785	95578;95579;95580	chr2:178545883;178545882;178545881	chr2:179410610;179410609;179410608
N2AB	30144	90655;90656;90657	chr2:178545883;178545882;178545881	chr2:179410610;179410609;179410608
N2A	29217	87874;87875;87876	chr2:178545883;178545882;178545881	chr2:179410610;179410609;179410608
N2B	22720	68383;68384;68385	chr2:178545883;178545882;178545881	chr2:179410610;179410609;179410608
Novex-1	22845	68758;68759;68760	chr2:178545883;178545882;178545881	chr2:179410610;179410609;179410608
Novex-2	22912	68959;68960;68961	chr2:178545883;178545882;178545881	chr2:179410610;179410609;179410608
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-119
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.1363
• 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/I	rs755742174	-0.744	0.767	N	0.322	0.187	0.53906709209	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
V/I	rs755742174	-0.744	0.767	N	0.322	0.187	0.53906709209	gnomAD-4.0.0	8.21039E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99473E-06	1.15931E-05	1.65662E-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
V/A	0.379	ambiguous	0.3901	ambiguous	-1.953	Destabilizing	0.998	D	0.453	neutral	N	0.489938155	None	None	N
V/C	0.7938	likely_pathogenic	0.7911	pathogenic	-1.709	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/D	0.9334	likely_pathogenic	0.9372	pathogenic	-2.792	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/E	0.6201	likely_pathogenic	0.6277	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.795	deleterious	N	0.473754951	None	None	N
V/F	0.5161	ambiguous	0.5032	ambiguous	-1.226	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/G	0.6571	likely_pathogenic	0.6733	pathogenic	-2.401	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.533516953	None	None	N
V/H	0.9088	likely_pathogenic	0.903	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/I	0.1195	likely_benign	0.11	benign	-0.732	Destabilizing	0.767	D	0.322	neutral	N	0.477581118	None	None	N
V/K	0.7585	likely_pathogenic	0.7566	pathogenic	-1.568	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/L	0.5955	likely_pathogenic	0.597	pathogenic	-0.732	Destabilizing	0.981	D	0.409	neutral	N	0.513585364	None	None	N
V/M	0.2877	likely_benign	0.2622	benign	-0.858	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
V/N	0.8175	likely_pathogenic	0.8112	pathogenic	-1.789	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/P	0.9948	likely_pathogenic	0.9953	pathogenic	-1.111	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Q	0.5552	ambiguous	0.5593	ambiguous	-1.762	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/R	0.6924	likely_pathogenic	0.6976	pathogenic	-1.279	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/S	0.5454	ambiguous	0.5305	ambiguous	-2.322	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/T	0.4483	ambiguous	0.3919	ambiguous	-2.057	Highly Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
V/W	0.9751	likely_pathogenic	0.9744	pathogenic	-1.701	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.8835	likely_pathogenic	0.8802	pathogenic	-1.358	Destabilizing	1.0	D	0.814	deleterious	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.