TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25732	77419;77420;77421	chr2:178568938;178568937;178568936	chr2:179433665;179433664;179433663
N2AB	24091	72496;72497;72498	chr2:178568938;178568937;178568936	chr2:179433665;179433664;179433663
N2A	23164	69715;69716;69717	chr2:178568938;178568937;178568936	chr2:179433665;179433664;179433663
N2B	16667	50224;50225;50226	chr2:178568938;178568937;178568936	chr2:179433665;179433664;179433663
Novex-1	16792	50599;50600;50601	chr2:178568938;178568937;178568936	chr2:179433665;179433664;179433663
Novex-2	16859	50800;50801;50802	chr2:178568938;178568937;178568936	chr2:179433665;179433664;179433663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-75
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.2312
• 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
Q/H	None	None	0.007	N	0.155	0.143	0.139678290688	gnomAD-4.0.0	6.84347E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99588E-07	0	0
Q/R	rs779015495	0.004	0.837	N	0.447	0.225	0.19670166235	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.69E-05	None	0	0	None	0	None	0	0	0
Q/R	rs779015495	0.004	0.837	N	0.447	0.225	0.19670166235	gnomAD-4.0.0	4.77599E-06	None	None	None	None	N	None	0	6.85965E-05	None	0	0	None	0	0	0	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
Q/A	0.2239	likely_benign	0.2394	benign	-0.732	Destabilizing	0.584	D	0.395	neutral	None	None	None	None	N
Q/C	0.5397	ambiguous	0.5799	pathogenic	-0.145	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	N
Q/D	0.3711	ambiguous	0.361	ambiguous	-0.751	Destabilizing	0.872	D	0.455	neutral	None	None	None	None	N
Q/E	0.0795	likely_benign	0.0795	benign	-0.541	Destabilizing	0.679	D	0.361	neutral	N	0.380471069	None	None	N
Q/F	0.7411	likely_pathogenic	0.7997	pathogenic	-0.108	Destabilizing	0.773	D	0.597	neutral	None	None	None	None	N
Q/G	0.1844	likely_benign	0.1898	benign	-1.168	Destabilizing	0.737	D	0.487	neutral	None	None	None	None	N
Q/H	0.1794	likely_benign	0.1823	benign	-0.714	Destabilizing	0.007	N	0.155	neutral	N	0.397056675	None	None	N
Q/I	0.7453	likely_pathogenic	0.7748	pathogenic	0.434	Stabilizing	0.932	D	0.658	neutral	None	None	None	None	N
Q/K	0.2736	likely_benign	0.2456	benign	-0.258	Destabilizing	0.679	D	0.426	neutral	N	0.414082211	None	None	N
Q/L	0.2271	likely_benign	0.2488	benign	0.434	Stabilizing	0.679	D	0.507	neutral	N	0.464204387	None	None	N
Q/M	0.4559	ambiguous	0.5163	ambiguous	0.622	Stabilizing	0.993	D	0.524	neutral	None	None	None	None	N
Q/N	0.2133	likely_benign	0.2401	benign	-0.971	Destabilizing	0.872	D	0.455	neutral	None	None	None	None	N
Q/P	0.8882	likely_pathogenic	0.8564	pathogenic	0.075	Stabilizing	0.912	D	0.623	neutral	N	0.512766338	None	None	N
Q/R	0.2202	likely_benign	0.2014	benign	-0.347	Destabilizing	0.837	D	0.447	neutral	N	0.429147664	None	None	N
Q/S	0.1569	likely_benign	0.1716	benign	-1.207	Destabilizing	0.1	N	0.161	neutral	None	None	None	None	N
Q/T	0.2657	likely_benign	0.2803	benign	-0.789	Destabilizing	0.773	D	0.514	neutral	None	None	None	None	N
Q/V	0.5367	ambiguous	0.5632	ambiguous	0.075	Stabilizing	0.872	D	0.579	neutral	None	None	None	None	N
Q/W	0.6661	likely_pathogenic	0.6807	pathogenic	-0.009	Destabilizing	0.995	D	0.574	neutral	None	None	None	None	N
Q/Y	0.4088	ambiguous	0.4431	ambiguous	0.282	Stabilizing	0.037	N	0.229	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.