TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28516	85771;85772;85773	chr2:178560586;178560585;178560584	chr2:179425313;179425312;179425311
N2AB	26875	80848;80849;80850	chr2:178560586;178560585;178560584	chr2:179425313;179425312;179425311
N2A	25948	78067;78068;78069	chr2:178560586;178560585;178560584	chr2:179425313;179425312;179425311
N2B	19451	58576;58577;58578	chr2:178560586;178560585;178560584	chr2:179425313;179425312;179425311
Novex-1	19576	58951;58952;58953	chr2:178560586;178560585;178560584	chr2:179425313;179425312;179425311
Novex-2	19643	59152;59153;59154	chr2:178560586;178560585;178560584	chr2:179425313;179425312;179425311
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-95
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6238
• 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
L/F	rs13026702	None	0.998	N	0.708	0.378	0.489036454283	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs13026702	None	0.998	N	0.708	0.378	0.489036454283	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47042E-05	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
L/A	0.6148	likely_pathogenic	0.608	pathogenic	-1.393	Destabilizing	0.968	D	0.564	neutral	None	None	None	None	N
L/C	0.7168	likely_pathogenic	0.7112	pathogenic	-0.869	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
L/D	0.9334	likely_pathogenic	0.9309	pathogenic	-0.591	Destabilizing	0.991	D	0.751	deleterious	None	None	None	None	N
L/E	0.6686	likely_pathogenic	0.6621	pathogenic	-0.595	Destabilizing	0.982	D	0.69	prob.neutral	None	None	None	None	N
L/F	0.3416	ambiguous	0.333	benign	-0.941	Destabilizing	0.998	D	0.708	prob.delet.	N	0.521983254	None	None	N
L/G	0.8207	likely_pathogenic	0.8215	pathogenic	-1.696	Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	N
L/H	0.4557	ambiguous	0.4185	ambiguous	-0.76	Destabilizing	0.998	D	0.717	prob.delet.	N	0.481016797	None	None	N
L/I	0.1522	likely_benign	0.1422	benign	-0.651	Destabilizing	0.979	D	0.478	neutral	N	0.420184251	None	None	N
L/K	0.3983	ambiguous	0.3721	ambiguous	-0.857	Destabilizing	0.982	D	0.661	neutral	None	None	None	None	N
L/M	0.199	likely_benign	0.2022	benign	-0.555	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
L/N	0.7307	likely_pathogenic	0.7158	pathogenic	-0.695	Destabilizing	0.991	D	0.755	deleterious	None	None	None	None	N
L/P	0.8083	likely_pathogenic	0.8441	pathogenic	-0.866	Destabilizing	0.994	D	0.761	deleterious	N	0.484637648	None	None	N
L/Q	0.2516	likely_benign	0.2294	benign	-0.854	Destabilizing	0.682	D	0.429	neutral	None	None	None	None	N
L/R	0.2921	likely_benign	0.2537	benign	-0.261	Destabilizing	0.976	D	0.739	prob.delet.	N	0.509339244	None	None	N
L/S	0.6779	likely_pathogenic	0.6666	pathogenic	-1.328	Destabilizing	0.991	D	0.672	neutral	None	None	None	None	N
L/T	0.5622	ambiguous	0.5556	ambiguous	-1.208	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
L/V	0.198	likely_benign	0.1848	benign	-0.866	Destabilizing	0.958	D	0.458	neutral	N	0.473093229	None	None	N
L/W	0.4493	ambiguous	0.4071	ambiguous	-0.972	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
L/Y	0.6188	likely_pathogenic	0.6005	pathogenic	-0.753	Destabilizing	0.998	D	0.751	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.