TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25852	77779;77780;77781	chr2:178568578;178568577;178568576	chr2:179433305;179433304;179433303
N2AB	24211	72856;72857;72858	chr2:178568578;178568577;178568576	chr2:179433305;179433304;179433303
N2A	23284	70075;70076;70077	chr2:178568578;178568577;178568576	chr2:179433305;179433304;179433303
N2B	16787	50584;50585;50586	chr2:178568578;178568577;178568576	chr2:179433305;179433304;179433303
Novex-1	16912	50959;50960;50961	chr2:178568578;178568577;178568576	chr2:179433305;179433304;179433303
Novex-2	16979	51160;51161;51162	chr2:178568578;178568577;178568576	chr2:179433305;179433304;179433303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-136
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1752
• 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/I	None	None	0.684	N	0.422	0.201	0.519514513453	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	2.77408E-05	None	0	0	0	0	0
L/V	None	None	0.684	N	0.417	0.252	0.542363599239	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85976E-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	0.1135	likely_benign	0.1109	benign	-1.772	Destabilizing	0.543	D	0.469	neutral	None	None	None	None	N
L/C	0.2008	likely_benign	0.1998	benign	-1.331	Destabilizing	0.996	D	0.514	neutral	None	None	None	None	N
L/D	0.4617	ambiguous	0.431	ambiguous	-1.864	Destabilizing	0.742	D	0.624	neutral	None	None	None	None	N
L/E	0.2268	likely_benign	0.2132	benign	-1.873	Destabilizing	0.59	D	0.583	neutral	None	None	None	None	N
L/F	0.0733	likely_benign	0.0682	benign	-1.496	Destabilizing	0.007	N	0.255	neutral	D	0.524650705	None	None	N
L/G	0.3031	likely_benign	0.2927	benign	-2.069	Highly Destabilizing	0.742	D	0.604	neutral	None	None	None	None	N
L/H	0.0847	likely_benign	0.0836	benign	-1.321	Destabilizing	0.007	N	0.41	neutral	N	0.471971013	None	None	N
L/I	0.0646	likely_benign	0.0611	benign	-1.022	Destabilizing	0.684	D	0.422	neutral	N	0.489612624	None	None	N
L/K	0.1271	likely_benign	0.1231	benign	-1.17	Destabilizing	0.59	D	0.553	neutral	None	None	None	None	N
L/M	0.0688	likely_benign	0.0676	benign	-0.822	Destabilizing	0.953	D	0.499	neutral	None	None	None	None	N
L/N	0.1772	likely_benign	0.1668	benign	-1.084	Destabilizing	0.742	D	0.627	neutral	None	None	None	None	N
L/P	0.895	likely_pathogenic	0.8933	pathogenic	-1.243	Destabilizing	0.939	D	0.639	neutral	D	0.524477346	None	None	N
L/Q	0.0775	likely_benign	0.077	benign	-1.352	Destabilizing	0.037	N	0.339	neutral	None	None	None	None	N
L/R	0.0913	likely_benign	0.0899	benign	-0.547	Destabilizing	0.521	D	0.602	neutral	N	0.489612624	None	None	N
L/S	0.1182	likely_benign	0.1096	benign	-1.636	Destabilizing	0.742	D	0.558	neutral	None	None	None	None	N
L/T	0.0832	likely_benign	0.0795	benign	-1.537	Destabilizing	0.742	D	0.513	neutral	None	None	None	None	N
L/V	0.0584	likely_benign	0.0568	benign	-1.243	Destabilizing	0.684	D	0.417	neutral	N	0.457790994	None	None	N
L/W	0.1578	likely_benign	0.1517	benign	-1.57	Destabilizing	0.996	D	0.591	neutral	None	None	None	None	N
L/Y	0.1604	likely_benign	0.1547	benign	-1.305	Destabilizing	0.59	D	0.515	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.