TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31516	94771;94772;94773	chr2:178546882;178546881;178546880	chr2:179411609;179411608;179411607
N2AB	29875	89848;89849;89850	chr2:178546882;178546881;178546880	chr2:179411609;179411608;179411607
N2A	28948	87067;87068;87069	chr2:178546882;178546881;178546880	chr2:179411609;179411608;179411607
N2B	22451	67576;67577;67578	chr2:178546882;178546881;178546880	chr2:179411609;179411608;179411607
Novex-1	22576	67951;67952;67953	chr2:178546882;178546881;178546880	chr2:179411609;179411608;179411607
Novex-2	22643	68152;68153;68154	chr2:178546882;178546881;178546880	chr2:179411609;179411608;179411607
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-118
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5228
• 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/A	None	None	0.996	N	0.491	0.288	0.324161360171	gnomAD-4.0.0	1.65131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.98093E-06	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	0.1332	likely_benign	0.1461	benign	-0.54	Destabilizing	0.996	D	0.491	neutral	N	0.501301337	None	None	N
T/C	0.4983	ambiguous	0.5173	ambiguous	-0.371	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.7664	likely_pathogenic	0.7589	pathogenic	0.472	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
T/E	0.5867	likely_pathogenic	0.5954	pathogenic	0.437	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
T/F	0.4266	ambiguous	0.468	ambiguous	-0.853	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
T/G	0.437	ambiguous	0.4451	ambiguous	-0.728	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
T/H	0.4784	ambiguous	0.5045	ambiguous	-0.937	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
T/I	0.245	likely_benign	0.2367	benign	-0.154	Destabilizing	0.999	D	0.717	prob.delet.	N	0.460012075	None	None	N
T/K	0.3295	likely_benign	0.3426	ambiguous	-0.334	Destabilizing	0.999	D	0.688	prob.neutral	N	0.515345283	None	None	N
T/L	0.149	likely_benign	0.1594	benign	-0.154	Destabilizing	0.994	D	0.6	neutral	None	None	None	None	N
T/M	0.0981	likely_benign	0.1061	benign	-0.044	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
T/N	0.3065	likely_benign	0.2981	benign	-0.232	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
T/P	0.7343	likely_pathogenic	0.7439	pathogenic	-0.252	Destabilizing	1.0	D	0.735	prob.delet.	N	0.489325363	None	None	N
T/Q	0.3672	ambiguous	0.3832	ambiguous	-0.384	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/R	0.2706	likely_benign	0.2882	benign	-0.12	Destabilizing	0.999	D	0.734	prob.delet.	N	0.483436333	None	None	N
T/S	0.1818	likely_benign	0.1824	benign	-0.543	Destabilizing	0.996	D	0.493	neutral	N	0.483192792	None	None	N
T/V	0.1778	likely_benign	0.1788	benign	-0.252	Destabilizing	0.994	D	0.556	neutral	None	None	None	None	N
T/W	0.7348	likely_pathogenic	0.7573	pathogenic	-0.812	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
T/Y	0.4753	ambiguous	0.5191	ambiguous	-0.54	Destabilizing	0.833	D	0.309	neutral	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.