TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17226	51901;51902;51903	chr2:178609747;178609746;178609745	chr2:179474474;179474473;179474472
N2AB	15585	46978;46979;46980	chr2:178609747;178609746;178609745	chr2:179474474;179474473;179474472
N2A	14658	44197;44198;44199	chr2:178609747;178609746;178609745	chr2:179474474;179474473;179474472
N2B	8161	24706;24707;24708	chr2:178609747;178609746;178609745	chr2:179474474;179474473;179474472
Novex-1	8286	25081;25082;25083	chr2:178609747;178609746;178609745	chr2:179474474;179474473;179474472
Novex-2	8353	25282;25283;25284	chr2:178609747;178609746;178609745	chr2:179474474;179474473;179474472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-13
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.1019
• 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
N/D	rs780947951	-2.53	0.999	D	0.617	0.672	0.433047596574	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/D	rs780947951	-2.53	0.999	D	0.617	0.672	0.433047596574	gnomAD-4.0.0	1.59391E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4348E-05	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
N/A	0.9977	likely_pathogenic	0.998	pathogenic	0.287	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
N/C	0.9876	likely_pathogenic	0.9897	pathogenic	-0.056	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
N/D	0.9946	likely_pathogenic	0.994	pathogenic	-2.252	Highly Destabilizing	0.999	D	0.617	neutral	D	0.533081971	None	None	N
N/E	0.9992	likely_pathogenic	0.999	pathogenic	-2.115	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
N/F	0.9997	likely_pathogenic	0.9996	pathogenic	0.029	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
N/G	0.9945	likely_pathogenic	0.9949	pathogenic	0.012	Stabilizing	0.999	D	0.577	neutral	None	None	None	None	N
N/H	0.9948	likely_pathogenic	0.9947	pathogenic	-0.002	Destabilizing	1.0	D	0.783	deleterious	D	0.545452235	None	None	N
N/I	0.9965	likely_pathogenic	0.9964	pathogenic	0.945	Stabilizing	1.0	D	0.797	deleterious	D	0.539375848	None	None	N
N/K	0.9993	likely_pathogenic	0.9991	pathogenic	0.321	Stabilizing	1.0	D	0.76	deleterious	D	0.529550026	None	None	N
N/L	0.9941	likely_pathogenic	0.9929	pathogenic	0.945	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/M	0.9954	likely_pathogenic	0.9953	pathogenic	1.085	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
N/P	0.9993	likely_pathogenic	0.9994	pathogenic	0.756	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/Q	0.9995	likely_pathogenic	0.9995	pathogenic	-0.753	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
N/R	0.9991	likely_pathogenic	0.9987	pathogenic	0.311	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/S	0.9675	likely_pathogenic	0.9704	pathogenic	-0.425	Destabilizing	0.999	D	0.6	neutral	N	0.505694871	None	None	N
N/T	0.9698	likely_pathogenic	0.9694	pathogenic	-0.156	Destabilizing	0.999	D	0.731	prob.delet.	N	0.507070316	None	None	N
N/V	0.9948	likely_pathogenic	0.9946	pathogenic	0.756	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.186	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
N/Y	0.9969	likely_pathogenic	0.996	pathogenic	0.43	Stabilizing	1.0	D	0.807	deleterious	D	0.55706203	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.