TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28729	86410;86411;86412	chr2:178559947;178559946;178559945	chr2:179424674;179424673;179424672
N2AB	27088	81487;81488;81489	chr2:178559947;178559946;178559945	chr2:179424674;179424673;179424672
N2A	26161	78706;78707;78708	chr2:178559947;178559946;178559945	chr2:179424674;179424673;179424672
N2B	19664	59215;59216;59217	chr2:178559947;178559946;178559945	chr2:179424674;179424673;179424672
Novex-1	19789	59590;59591;59592	chr2:178559947;178559946;178559945	chr2:179424674;179424673;179424672
Novex-2	19856	59791;59792;59793	chr2:178559947;178559946;178559945	chr2:179424674;179424673;179424672
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-97
• Domain position: 79
• Structural Position: 112
• Q(SASA): 0.0971
• 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/S	rs1703025837	None	0.999	N	0.593	0.514	0.283371740733	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	1.47E-05	0	0
N/S	rs1703025837	None	0.999	N	0.593	0.514	0.283371740733	gnomAD-4.0.0	8.05601E-06	None	None	None	None	N	None	0	0	None	0	2.45284E-04	None	0	0	8.4759E-07	0	1.60113E-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
N/A	0.9729	likely_pathogenic	0.9882	pathogenic	-0.884	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/C	0.7952	likely_pathogenic	0.8725	pathogenic	-0.533	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
N/D	0.977	likely_pathogenic	0.985	pathogenic	-1.978	Destabilizing	0.999	D	0.613	neutral	N	0.520738161	None	None	N
N/E	0.9966	likely_pathogenic	0.9976	pathogenic	-1.805	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
N/F	0.9979	likely_pathogenic	0.9986	pathogenic	-0.569	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
N/G	0.9333	likely_pathogenic	0.9645	pathogenic	-1.226	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
N/H	0.9381	likely_pathogenic	0.9602	pathogenic	-0.888	Destabilizing	1.0	D	0.786	deleterious	D	0.551212679	None	None	N
N/I	0.9787	likely_pathogenic	0.9858	pathogenic	0.001	Stabilizing	1.0	D	0.769	deleterious	D	0.551719659	None	None	N
N/K	0.9954	likely_pathogenic	0.9969	pathogenic	-0.41	Destabilizing	1.0	D	0.759	deleterious	D	0.532347956	None	None	N
N/L	0.9323	likely_pathogenic	0.9487	pathogenic	0.001	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
N/M	0.9779	likely_pathogenic	0.9861	pathogenic	0.224	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
N/P	0.9927	likely_pathogenic	0.9954	pathogenic	-0.267	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
N/Q	0.9924	likely_pathogenic	0.9953	pathogenic	-1.149	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
N/R	0.9906	likely_pathogenic	0.9927	pathogenic	-0.447	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
N/S	0.4461	ambiguous	0.6126	pathogenic	-1.194	Destabilizing	0.999	D	0.593	neutral	N	0.501086516	None	None	N
N/T	0.8198	likely_pathogenic	0.8998	pathogenic	-0.861	Destabilizing	0.999	D	0.727	prob.delet.	N	0.507399484	None	None	N
N/V	0.9639	likely_pathogenic	0.9779	pathogenic	-0.267	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
N/W	0.999	likely_pathogenic	0.9994	pathogenic	-0.499	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
N/Y	0.982	likely_pathogenic	0.9858	pathogenic	-0.143	Destabilizing	1.0	D	0.785	deleterious	D	0.533361914	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.