TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18716	56371;56372;56373	chr2:178599755;178599754;178599753	chr2:179464482;179464481;179464480
N2AB	17075	51448;51449;51450	chr2:178599755;178599754;178599753	chr2:179464482;179464481;179464480
N2A	16148	48667;48668;48669	chr2:178599755;178599754;178599753	chr2:179464482;179464481;179464480
N2B	9651	29176;29177;29178	chr2:178599755;178599754;178599753	chr2:179464482;179464481;179464480
Novex-1	9776	29551;29552;29553	chr2:178599755;178599754;178599753	chr2:179464482;179464481;179464480
Novex-2	9843	29752;29753;29754	chr2:178599755;178599754;178599753	chr2:179464482;179464481;179464480
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-116
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.302
• 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
L/V	rs1216121898	None	0.999	N	0.625	0.243	0.403896168776	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs1216121898	None	0.999	N	0.625	0.243	0.403896168776	gnomAD-4.0.0	2.5658E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.79209E-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	0.7125	likely_pathogenic	0.6767	pathogenic	-2.17	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
L/C	0.7451	likely_pathogenic	0.7213	pathogenic	-1.39	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
L/D	0.9952	likely_pathogenic	0.9937	pathogenic	-1.805	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
L/E	0.9676	likely_pathogenic	0.9601	pathogenic	-1.708	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
L/F	0.5737	likely_pathogenic	0.52	ambiguous	-1.364	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
L/G	0.9661	likely_pathogenic	0.9531	pathogenic	-2.598	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
L/H	0.9334	likely_pathogenic	0.914	pathogenic	-1.752	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
L/I	0.0983	likely_benign	0.0962	benign	-1.003	Destabilizing	0.999	D	0.615	neutral	N	0.416861518	None	None	I
L/K	0.9463	likely_pathogenic	0.9317	pathogenic	-1.679	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
L/M	0.2178	likely_benign	0.21	benign	-0.806	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
L/N	0.9654	likely_pathogenic	0.9553	pathogenic	-1.627	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
L/P	0.942	likely_pathogenic	0.9256	pathogenic	-1.366	Destabilizing	1.0	D	0.858	deleterious	N	0.520499396	None	None	I
L/Q	0.8978	likely_pathogenic	0.8767	pathogenic	-1.681	Destabilizing	1.0	D	0.879	deleterious	N	0.508978506	None	None	I
L/R	0.9251	likely_pathogenic	0.8973	pathogenic	-1.147	Destabilizing	1.0	D	0.875	deleterious	N	0.508978506	None	None	I
L/S	0.9251	likely_pathogenic	0.9048	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
L/T	0.7135	likely_pathogenic	0.6878	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
L/V	0.0935	likely_benign	0.0938	benign	-1.366	Destabilizing	0.999	D	0.625	neutral	N	0.43247597	None	None	I
L/W	0.9153	likely_pathogenic	0.8804	pathogenic	-1.513	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
L/Y	0.9052	likely_pathogenic	0.8824	pathogenic	-1.304	Destabilizing	1.0	D	0.803	deleterious	None	None	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.