TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35489	106690;106691;106692	chr2:178530026;178530025;178530024	chr2:179394753;179394752;179394751
N2AB	33848	101767;101768;101769	chr2:178530026;178530025;178530024	chr2:179394753;179394752;179394751
N2A	32921	98986;98987;98988	chr2:178530026;178530025;178530024	chr2:179394753;179394752;179394751
N2B	26424	79495;79496;79497	chr2:178530026;178530025;178530024	chr2:179394753;179394752;179394751
Novex-1	26549	79870;79871;79872	chr2:178530026;178530025;178530024	chr2:179394753;179394752;179394751
Novex-2	26616	80071;80072;80073	chr2:178530026;178530025;178530024	chr2:179394753;179394752;179394751
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-166
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.2942
• 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/H	rs767087308	-1.03	0.999	N	0.744	0.289	0.832902513328	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
L/H	rs767087308	-1.03	0.999	N	0.744	0.289	0.832902513328	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/H	rs767087308	-1.03	0.999	N	0.744	0.289	0.832902513328	gnomAD-4.0.0	9.01121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.67834E-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	0.2535	likely_benign	0.2655	benign	-1.38	Destabilizing	0.84	D	0.592	neutral	None	None	None	None	N
L/C	0.6346	likely_pathogenic	0.5808	pathogenic	-0.929	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
L/D	0.4946	ambiguous	0.4976	ambiguous	-0.398	Destabilizing	0.989	D	0.759	deleterious	None	None	None	None	N
L/E	0.2906	likely_benign	0.2887	benign	-0.42	Destabilizing	0.989	D	0.747	deleterious	None	None	None	None	N
L/F	0.1403	likely_benign	0.1345	benign	-1.126	Destabilizing	0.986	D	0.633	neutral	N	0.474107241	None	None	N
L/G	0.4958	ambiguous	0.5097	ambiguous	-1.66	Destabilizing	0.989	D	0.718	prob.delet.	None	None	None	None	N
L/H	0.2166	likely_benign	0.2051	benign	-0.899	Destabilizing	0.999	D	0.744	deleterious	N	0.496021309	None	None	N
L/I	0.0828	likely_benign	0.084	benign	-0.707	Destabilizing	0.664	D	0.545	neutral	N	0.456193484	None	None	N
L/K	0.2386	likely_benign	0.2402	benign	-0.636	Destabilizing	0.989	D	0.709	prob.delet.	None	None	None	None	N
L/M	0.1451	likely_benign	0.1455	benign	-0.532	Destabilizing	0.989	D	0.649	neutral	None	None	None	None	N
L/N	0.2344	likely_benign	0.2442	benign	-0.403	Destabilizing	0.989	D	0.759	deleterious	None	None	None	None	N
L/P	0.4525	ambiguous	0.4677	ambiguous	-0.899	Destabilizing	0.995	D	0.761	deleterious	D	0.528651015	None	None	N
L/Q	0.16	likely_benign	0.1642	benign	-0.61	Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	N
L/R	0.1845	likely_benign	0.1854	benign	-0.128	Destabilizing	0.986	D	0.76	deleterious	N	0.432220546	None	None	N
L/S	0.2145	likely_benign	0.2248	benign	-1.101	Destabilizing	0.864	D	0.653	neutral	None	None	None	None	N
L/T	0.1755	likely_benign	0.1823	benign	-1.002	Destabilizing	0.145	N	0.348	neutral	None	None	None	None	N
L/V	0.1051	likely_benign	0.1076	benign	-0.899	Destabilizing	0.114	N	0.233	neutral	N	0.424313139	None	None	N
L/W	0.2902	likely_benign	0.2683	benign	-1.124	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
L/Y	0.3167	likely_benign	0.2979	benign	-0.87	Destabilizing	0.996	D	0.723	prob.delet.	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.