TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22112	66559;66560;66561	chr2:178582035;178582034;178582033	chr2:179446762;179446761;179446760
N2AB	20471	61636;61637;61638	chr2:178582035;178582034;178582033	chr2:179446762;179446761;179446760
N2A	19544	58855;58856;58857	chr2:178582035;178582034;178582033	chr2:179446762;179446761;179446760
N2B	13047	39364;39365;39366	chr2:178582035;178582034;178582033	chr2:179446762;179446761;179446760
Novex-1	13172	39739;39740;39741	chr2:178582035;178582034;178582033	chr2:179446762;179446761;179446760
Novex-2	13239	39940;39941;39942	chr2:178582035;178582034;178582033	chr2:179446762;179446761;179446760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-48
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.5845
• Predicted PPI site: I

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
E/Q	None	None	0.946	N	0.465	0.17	0.212008924253	gnomAD-4.0.0	1.59214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43295E-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
E/A	0.5892	likely_pathogenic	0.468	ambiguous	-0.185	Destabilizing	0.896	D	0.516	neutral	N	0.475960176	None	None	I
E/C	0.9724	likely_pathogenic	0.9567	pathogenic	-0.337	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
E/D	0.1578	likely_benign	0.1365	benign	-0.605	Destabilizing	0.004	N	0.174	neutral	N	0.432516043	None	None	I
E/F	0.9755	likely_pathogenic	0.9554	pathogenic	0.427	Stabilizing	0.996	D	0.654	neutral	None	None	None	None	I
E/G	0.5157	ambiguous	0.4138	ambiguous	-0.472	Destabilizing	0.896	D	0.522	neutral	N	0.4932765	None	None	I
E/H	0.9032	likely_pathogenic	0.826	pathogenic	0.795	Stabilizing	0.996	D	0.533	neutral	None	None	None	None	I
E/I	0.9123	likely_pathogenic	0.8328	pathogenic	0.569	Stabilizing	0.988	D	0.649	neutral	None	None	None	None	I
E/K	0.7537	likely_pathogenic	0.5962	pathogenic	0.274	Stabilizing	0.896	D	0.497	neutral	N	0.483694224	None	None	I
E/L	0.8896	likely_pathogenic	0.8022	pathogenic	0.569	Stabilizing	0.988	D	0.623	neutral	None	None	None	None	I
E/M	0.9272	likely_pathogenic	0.8681	pathogenic	0.416	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	I
E/N	0.6486	likely_pathogenic	0.5341	ambiguous	-0.516	Destabilizing	0.851	D	0.491	neutral	None	None	None	None	I
E/P	0.9222	likely_pathogenic	0.8845	pathogenic	0.339	Stabilizing	0.988	D	0.547	neutral	None	None	None	None	I
E/Q	0.5128	ambiguous	0.3749	ambiguous	-0.369	Destabilizing	0.946	D	0.465	neutral	N	0.492564424	None	None	I
E/R	0.8334	likely_pathogenic	0.7306	pathogenic	0.693	Stabilizing	0.988	D	0.516	neutral	None	None	None	None	I
E/S	0.5737	likely_pathogenic	0.4645	ambiguous	-0.644	Destabilizing	0.919	D	0.489	neutral	None	None	None	None	I
E/T	0.7089	likely_pathogenic	0.5674	pathogenic	-0.38	Destabilizing	0.959	D	0.519	neutral	None	None	None	None	I
E/V	0.7999	likely_pathogenic	0.6654	pathogenic	0.339	Stabilizing	0.984	D	0.555	neutral	N	0.505571007	None	None	I
E/W	0.9898	likely_pathogenic	0.9828	pathogenic	0.664	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
E/Y	0.9397	likely_pathogenic	0.8978	pathogenic	0.706	Stabilizing	0.996	D	0.643	neutral	None	None	None	None	I

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.