TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9228	27907;27908;27909	chr2:178712148;178712147;178712146	chr2:179576875;179576874;179576873
N2AB	8911	26956;26957;26958	chr2:178712148;178712147;178712146	chr2:179576875;179576874;179576873
N2A	7984	24175;24176;24177	chr2:178712148;178712147;178712146	chr2:179576875;179576874;179576873
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-78
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.122
• 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/P	rs756143599	-1.866	0.741	N	0.823	0.515	0.786464674917	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/P	rs756143599	-1.866	0.741	N	0.823	0.515	0.786464674917	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs756143599	-1.866	0.741	N	0.823	0.515	0.786464674917	gnomAD-4.0.0	7.68628E-06	None	None	None	None	N	None	1.69073E-05	0	None	0	0	None	0	0	1.19644E-05	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	0.6424	likely_pathogenic	0.7135	pathogenic	-2.618	Highly Destabilizing	0.035	N	0.623	neutral	None	None	None	None	N
L/C	0.8139	likely_pathogenic	0.8556	pathogenic	-1.462	Destabilizing	0.824	D	0.769	deleterious	None	None	None	None	N
L/D	0.9934	likely_pathogenic	0.9954	pathogenic	-3.144	Highly Destabilizing	0.555	D	0.823	deleterious	None	None	None	None	N
L/E	0.9626	likely_pathogenic	0.9727	pathogenic	-2.845	Highly Destabilizing	0.555	D	0.797	deleterious	None	None	None	None	N
L/F	0.3348	likely_benign	0.4019	ambiguous	-1.581	Destabilizing	0.317	N	0.729	prob.delet.	N	0.457310992	None	None	N
L/G	0.9424	likely_pathogenic	0.9579	pathogenic	-3.198	Highly Destabilizing	0.555	D	0.797	deleterious	None	None	None	None	N
L/H	0.9303	likely_pathogenic	0.9516	pathogenic	-2.808	Highly Destabilizing	0.915	D	0.801	deleterious	N	0.513761707	None	None	N
L/I	0.061	likely_benign	0.0601	benign	-0.881	Destabilizing	None	N	0.219	neutral	N	0.363203178	None	None	N
L/K	0.9638	likely_pathogenic	0.9691	pathogenic	-1.834	Destabilizing	0.555	D	0.781	deleterious	None	None	None	None	N
L/M	0.1883	likely_benign	0.2016	benign	-0.817	Destabilizing	0.38	N	0.695	prob.neutral	None	None	None	None	N
L/N	0.9661	likely_pathogenic	0.9683	pathogenic	-2.443	Highly Destabilizing	0.791	D	0.827	deleterious	None	None	None	None	N
L/P	0.9446	likely_pathogenic	0.9739	pathogenic	-1.45	Destabilizing	0.741	D	0.823	deleterious	N	0.437533152	None	None	N
L/Q	0.9145	likely_pathogenic	0.9388	pathogenic	-2.155	Highly Destabilizing	0.791	D	0.8	deleterious	None	None	None	None	N
L/R	0.9318	likely_pathogenic	0.9531	pathogenic	-1.806	Destabilizing	0.484	N	0.805	deleterious	N	0.513761707	None	None	N
L/S	0.9062	likely_pathogenic	0.9248	pathogenic	-3.021	Highly Destabilizing	0.149	N	0.765	deleterious	None	None	None	None	N
L/T	0.645	likely_pathogenic	0.6494	pathogenic	-2.572	Highly Destabilizing	0.149	N	0.703	prob.neutral	None	None	None	None	N
L/V	0.062	likely_benign	0.0717	benign	-1.45	Destabilizing	None	N	0.23	neutral	N	0.288121056	None	None	N
L/W	0.852	likely_pathogenic	0.9078	pathogenic	-2.022	Highly Destabilizing	0.935	D	0.774	deleterious	None	None	None	None	N
L/Y	0.8777	likely_pathogenic	0.9046	pathogenic	-1.75	Destabilizing	0.555	D	0.779	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.