TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16656	50191;50192;50193	chr2:178612559;178612558;178612557	chr2:179477286;179477285;179477284
N2AB	15015	45268;45269;45270	chr2:178612559;178612558;178612557	chr2:179477286;179477285;179477284
N2A	14088	42487;42488;42489	chr2:178612559;178612558;178612557	chr2:179477286;179477285;179477284
N2B	7591	22996;22997;22998	chr2:178612559;178612558;178612557	chr2:179477286;179477285;179477284
Novex-1	7716	23371;23372;23373	chr2:178612559;178612558;178612557	chr2:179477286;179477285;179477284
Novex-2	7783	23572;23573;23574	chr2:178612559;178612558;178612557	chr2:179477286;179477285;179477284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-9
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.6262
• 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
R/C	rs1030093239	-0.258	0.252	D	0.517	0.268	0.514866526686	gnomAD-2.1.1	7.35E-06	None	None	None	None	N	None	4.21E-05	0	None	0	0	None	0	None	0	8.13E-06	0
R/C	rs1030093239	-0.258	0.252	D	0.517	0.268	0.514866526686	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	2.0816E-04	0
R/C	rs1030093239	-0.258	0.252	D	0.517	0.268	0.514866526686	gnomAD-4.0.0	1.11796E-05	None	None	None	None	N	None	1.33976E-05	0	None	0	0	None	0	0	1.01805E-05	4.42165E-05	1.60539E-05
R/H	rs373799076	-1.201	1.0	D	0.647	0.382	None	gnomAD-2.1.1	3.32E-05	None	None	None	None	N	None	0	2.95E-05	None	0	2.85812E-04	None	0	None	0	1.86E-05	0
R/H	rs373799076	-1.201	1.0	D	0.647	0.382	None	gnomAD-3.1.2	6.61E-06	None	None	None	None	N	None	2.43E-05	0	0	0	0	None	0	0	0	0	0
R/H	rs373799076	-1.201	1.0	D	0.647	0.382	None	gnomAD-4.0.0	3.04448E-05	None	None	None	None	N	None	2.68039E-05	3.35762E-05	None	0	4.49762E-05	None	0	0	3.47887E-05	1.10735E-05	1.60498E-05
R/L	rs373799076	None	0.913	N	0.707	0.306	0.552656131934	gnomAD-4.0.0	6.17284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.10304E-06	0	0
R/S	rs1030093239	-0.465	0.954	N	0.719	0.332	0.394536629495	gnomAD-2.1.1	8.3E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.71E-05	None	0	0	0
R/S	rs1030093239	-0.465	0.954	N	0.719	0.332	0.394536629495	gnomAD-4.0.0	5.48543E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80046E-06	5.83703E-05	1.66091E-05

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
R/A	0.7238	likely_pathogenic	0.8312	pathogenic	-0.896	Destabilizing	0.845	D	0.687	prob.neutral	None	None	None	None	N
R/C	0.4269	ambiguous	0.5644	pathogenic	-0.693	Destabilizing	0.252	N	0.517	neutral	D	0.576679243	None	None	N
R/D	0.9233	likely_pathogenic	0.9586	pathogenic	-0.207	Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
R/E	0.6306	likely_pathogenic	0.7742	pathogenic	-0.016	Destabilizing	0.985	D	0.659	neutral	None	None	None	None	N
R/F	0.8728	likely_pathogenic	0.9457	pathogenic	-0.302	Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	N
R/G	0.661	likely_pathogenic	0.7686	pathogenic	-1.277	Destabilizing	0.977	D	0.717	prob.delet.	N	0.477832869	None	None	N
R/H	0.2806	likely_benign	0.3524	ambiguous	-1.601	Destabilizing	1.0	D	0.647	neutral	D	0.562624057	None	None	N
R/I	0.5627	ambiguous	0.7917	pathogenic	0.164	Stabilizing	0.975	D	0.78	deleterious	None	None	None	None	N
R/K	0.2116	likely_benign	0.2167	benign	-0.687	Destabilizing	0.957	D	0.577	neutral	None	None	None	None	N
R/L	0.5086	ambiguous	0.6977	pathogenic	0.164	Stabilizing	0.913	D	0.707	prob.neutral	N	0.483117192	None	None	N
R/M	0.6713	likely_pathogenic	0.8238	pathogenic	-0.325	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
R/N	0.8637	likely_pathogenic	0.9178	pathogenic	-0.456	Destabilizing	0.996	D	0.652	neutral	None	None	None	None	N
R/P	0.9438	likely_pathogenic	0.964	pathogenic	-0.17	Destabilizing	0.998	D	0.787	deleterious	D	0.551071485	None	None	N
R/Q	0.196	likely_benign	0.2503	benign	-0.394	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
R/S	0.7893	likely_pathogenic	0.8815	pathogenic	-1.149	Destabilizing	0.954	D	0.719	prob.delet.	N	0.479378498	None	None	N
R/T	0.5914	likely_pathogenic	0.7666	pathogenic	-0.743	Destabilizing	0.916	D	0.72	prob.delet.	None	None	None	None	N
R/V	0.628	likely_pathogenic	0.7996	pathogenic	-0.17	Destabilizing	0.975	D	0.729	prob.delet.	None	None	None	None	N
R/W	0.5775	likely_pathogenic	0.7659	pathogenic	0.056	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
R/Y	0.7752	likely_pathogenic	0.8745	pathogenic	0.278	Stabilizing	0.996	D	0.792	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.