TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29966	90121;90122;90123	chr2:178553004;178553003;178553002	chr2:179417731;179417730;179417729
N2AB	28325	85198;85199;85200	chr2:178553004;178553003;178553002	chr2:179417731;179417730;179417729
N2A	27398	82417;82418;82419	chr2:178553004;178553003;178553002	chr2:179417731;179417730;179417729
N2B	20901	62926;62927;62928	chr2:178553004;178553003;178553002	chr2:179417731;179417730;179417729
Novex-1	21026	63301;63302;63303	chr2:178553004;178553003;178553002	chr2:179417731;179417730;179417729
Novex-2	21093	63502;63503;63504	chr2:178553004;178553003;178553002	chr2:179417731;179417730;179417729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-106
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3338
• 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
I/M	rs776286853	-0.388	0.794	N	0.303	0.111	0.437741185291	gnomAD-2.1.1	8.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
I/M	rs776286853	-0.388	0.794	N	0.303	0.111	0.437741185291	gnomAD-4.0.0	2.05539E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31889E-05	1.65695E-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
I/A	0.2331	likely_benign	0.2085	benign	-0.971	Destabilizing	0.061	N	0.212	neutral	None	None	None	None	I
I/C	0.5253	ambiguous	0.4985	ambiguous	-0.646	Destabilizing	0.94	D	0.357	neutral	None	None	None	None	I
I/D	0.6129	likely_pathogenic	0.5854	pathogenic	-0.584	Destabilizing	0.418	N	0.364	neutral	None	None	None	None	I
I/E	0.4158	ambiguous	0.3995	ambiguous	-0.677	Destabilizing	0.418	N	0.376	neutral	None	None	None	None	I
I/F	0.1589	likely_benign	0.1381	benign	-0.91	Destabilizing	0.523	D	0.283	neutral	N	0.506936444	None	None	I
I/G	0.4396	ambiguous	0.4191	ambiguous	-1.162	Destabilizing	0.228	N	0.348	neutral	None	None	None	None	I
I/H	0.2799	likely_benign	0.2576	benign	-0.36	Destabilizing	0.94	D	0.327	neutral	None	None	None	None	I
I/K	0.1534	likely_benign	0.1472	benign	-0.594	Destabilizing	0.418	N	0.375	neutral	None	None	None	None	I
I/L	0.0888	likely_benign	0.0856	benign	-0.579	Destabilizing	0.047	N	0.151	neutral	N	0.412908775	None	None	I
I/M	0.0913	likely_benign	0.0853	benign	-0.434	Destabilizing	0.794	D	0.303	neutral	N	0.46778341	None	None	I
I/N	0.1547	likely_benign	0.145	benign	-0.341	Destabilizing	0.351	N	0.361	neutral	N	0.454160751	None	None	I
I/P	0.8608	likely_pathogenic	0.8274	pathogenic	-0.676	Destabilizing	0.593	D	0.417	neutral	None	None	None	None	I
I/Q	0.2309	likely_benign	0.2137	benign	-0.626	Destabilizing	0.836	D	0.417	neutral	None	None	None	None	I
I/R	0.1369	likely_benign	0.1224	benign	0.087	Stabilizing	0.418	N	0.393	neutral	None	None	None	None	I
I/S	0.164	likely_benign	0.1556	benign	-0.804	Destabilizing	0.009	N	0.141	neutral	N	0.392880219	None	None	I
I/T	0.0943	likely_benign	0.0871	benign	-0.791	Destabilizing	None	N	0.117	neutral	N	0.338005584	None	None	I
I/V	0.0765	likely_benign	0.0736	benign	-0.676	Destabilizing	0.047	N	0.163	neutral	N	0.466049826	None	None	I
I/W	0.7035	likely_pathogenic	0.6689	pathogenic	-0.892	Destabilizing	0.983	D	0.32	neutral	None	None	None	None	I
I/Y	0.4114	ambiguous	0.3834	ambiguous	-0.671	Destabilizing	0.836	D	0.412	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.