TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16841	50746;50747;50748	chr2:178611788;178611787;178611786	chr2:179476515;179476514;179476513
N2AB	15200	45823;45824;45825	chr2:178611788;178611787;178611786	chr2:179476515;179476514;179476513
N2A	14273	43042;43043;43044	chr2:178611788;178611787;178611786	chr2:179476515;179476514;179476513
N2B	7776	23551;23552;23553	chr2:178611788;178611787;178611786	chr2:179476515;179476514;179476513
Novex-1	7901	23926;23927;23928	chr2:178611788;178611787;178611786	chr2:179476515;179476514;179476513
Novex-2	7968	24127;24128;24129	chr2:178611788;178611787;178611786	chr2:179476515;179476514;179476513
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: Fn3-10
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.9112
• 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
T/I	None	None	0.287	N	0.636	0.277	0.266385636622	gnomAD-4.0.0	1.59379E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86225E-06	0	0
T/R	None	None	0.943	D	0.663	0.428	0.404592120364	gnomAD-4.0.0	1.59379E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86225E-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	0.4522	ambiguous	0.4726	ambiguous	-0.847	Destabilizing	0.539	D	0.443	neutral	N	0.465517708	None	None	I
T/C	0.8763	likely_pathogenic	0.8963	pathogenic	-0.557	Destabilizing	0.988	D	0.667	prob.neutral	None	None	None	None	I
T/D	0.9726	likely_pathogenic	0.9741	pathogenic	-0.595	Destabilizing	0.956	D	0.718	prob.delet.	None	None	None	None	I
T/E	0.9747	likely_pathogenic	0.9749	pathogenic	-0.448	Destabilizing	0.956	D	0.667	prob.neutral	None	None	None	None	I
T/F	0.9769	likely_pathogenic	0.9755	pathogenic	-0.526	Destabilizing	0.916	D	0.667	prob.neutral	None	None	None	None	I
T/G	0.7222	likely_pathogenic	0.7369	pathogenic	-1.241	Destabilizing	0.956	D	0.516	neutral	None	None	None	None	I
T/H	0.9721	likely_pathogenic	0.9668	pathogenic	-1.363	Destabilizing	0.996	D	0.634	neutral	None	None	None	None	I
T/I	0.9203	likely_pathogenic	0.9269	pathogenic	0.161	Stabilizing	0.287	N	0.636	neutral	N	0.51478125	None	None	I
T/K	0.976	likely_pathogenic	0.97	pathogenic	-0.544	Destabilizing	0.943	D	0.692	prob.delet.	D	0.576883557	None	None	I
T/L	0.6437	likely_pathogenic	0.6771	pathogenic	0.161	Stabilizing	0.607	D	0.505	neutral	None	None	None	None	I
T/M	0.5465	ambiguous	0.5532	ambiguous	0.107	Stabilizing	0.976	D	0.658	prob.neutral	None	None	None	None	I
T/N	0.8348	likely_pathogenic	0.8208	pathogenic	-0.969	Destabilizing	0.985	D	0.698	prob.delet.	None	None	None	None	I
T/P	0.9073	likely_pathogenic	0.904	pathogenic	-0.141	Destabilizing	0.981	D	0.684	prob.delet.	D	0.536656283	None	None	I
T/Q	0.954	likely_pathogenic	0.9489	pathogenic	-0.804	Destabilizing	0.985	D	0.676	prob.neutral	None	None	None	None	I
T/R	0.9658	likely_pathogenic	0.9591	pathogenic	-0.657	Destabilizing	0.943	D	0.663	prob.neutral	D	0.576883557	None	None	I
T/S	0.3828	ambiguous	0.3383	benign	-1.255	Destabilizing	0.7	D	0.45	neutral	N	0.430104503	None	None	I
T/V	0.7347	likely_pathogenic	0.7624	pathogenic	-0.141	Destabilizing	0.01	N	0.309	neutral	None	None	None	None	I
T/W	0.9935	likely_pathogenic	0.9932	pathogenic	-0.622	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	I
T/Y	0.9856	likely_pathogenic	0.9847	pathogenic	-0.278	Destabilizing	0.956	D	0.664	prob.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.