TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27035	81328;81329;81330	chr2:178565029;178565028;178565027	chr2:179429756;179429755;179429754
N2AB	25394	76405;76406;76407	chr2:178565029;178565028;178565027	chr2:179429756;179429755;179429754
N2A	24467	73624;73625;73626	chr2:178565029;178565028;178565027	chr2:179429756;179429755;179429754
N2B	17970	54133;54134;54135	chr2:178565029;178565028;178565027	chr2:179429756;179429755;179429754
Novex-1	18095	54508;54509;54510	chr2:178565029;178565028;178565027	chr2:179429756;179429755;179429754
Novex-2	18162	54709;54710;54711	chr2:178565029;178565028;178565027	chr2:179429756;179429755;179429754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-84
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.3866
• 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
T/S	rs1705169163	None	None	N	0.179	0.058	0.137902524267	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/S	rs1705169163	None	None	N	0.179	0.058	0.137902524267	gnomAD-4.0.0	6.57575E-06	None	None	None	None	N	None	0	6.55824E-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
T/A	0.0882	likely_benign	0.0788	benign	-0.601	Destabilizing	0.055	N	0.443	neutral	N	0.519599096	None	None	N
T/C	0.3288	likely_benign	0.2894	benign	-0.459	Destabilizing	0.909	D	0.693	prob.neutral	None	None	None	None	N
T/D	0.6461	likely_pathogenic	0.6417	pathogenic	0.094	Stabilizing	0.157	N	0.602	neutral	None	None	None	None	N
T/E	0.5934	likely_pathogenic	0.5956	pathogenic	0.114	Stabilizing	0.157	N	0.605	neutral	None	None	None	None	N
T/F	0.3833	ambiguous	0.3269	benign	-0.645	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	N
T/G	0.1638	likely_benign	0.1192	benign	-0.862	Destabilizing	0.157	N	0.607	neutral	None	None	None	None	N
T/H	0.3708	ambiguous	0.3524	ambiguous	-1.032	Destabilizing	0.909	D	0.729	prob.delet.	None	None	None	None	N
T/I	0.2681	likely_benign	0.2026	benign	0.003	Stabilizing	0.497	N	0.695	prob.neutral	N	0.484325387	None	None	N
T/K	0.4194	ambiguous	0.4447	ambiguous	-0.564	Destabilizing	0.157	N	0.601	neutral	None	None	None	None	N
T/L	0.1171	likely_benign	0.1014	benign	0.003	Stabilizing	0.272	N	0.605	neutral	None	None	None	None	N
T/M	0.1083	likely_benign	0.0946	benign	-0.032	Destabilizing	0.968	D	0.689	prob.neutral	None	None	None	None	N
T/N	0.1314	likely_benign	0.1178	benign	-0.59	Destabilizing	0.124	N	0.522	neutral	N	0.477271041	None	None	N
T/P	0.0832	likely_benign	0.0749	benign	-0.165	Destabilizing	0.002	N	0.323	neutral	N	0.51925238	None	None	N
T/Q	0.3279	likely_benign	0.3169	benign	-0.643	Destabilizing	0.567	D	0.707	prob.neutral	None	None	None	None	N
T/R	0.3785	ambiguous	0.4125	ambiguous	-0.389	Destabilizing	0.567	D	0.698	prob.neutral	None	None	None	None	N
T/S	0.103	likely_benign	0.0905	benign	-0.856	Destabilizing	None	N	0.179	neutral	N	0.45547026	None	None	N
T/V	0.1754	likely_benign	0.1414	benign	-0.165	Destabilizing	0.272	N	0.501	neutral	None	None	None	None	N
T/W	0.7096	likely_pathogenic	0.6615	pathogenic	-0.655	Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	N
T/Y	0.3992	ambiguous	0.352	ambiguous	-0.382	Destabilizing	0.726	D	0.737	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.