TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4021	12286;12287;12288	chr2:178741172;178741171;178741170	chr2:179605899;179605898;179605897
N2AB	3704	11335;11336;11337	chr2:178741172;178741171;178741170	chr2:179605899;179605898;179605897
N2A	None	None	chr2:None	chr2:None
N2B	3658	11197;11198;11199	chr2:178741172;178741171;178741170	chr2:179605899;179605898;179605897
Novex-1	3783	11572;11573;11574	chr2:178741172;178741171;178741170	chr2:179605899;179605898;179605897
Novex-2	3850	11773;11774;11775	chr2:178741172;178741171;178741170	chr2:179605899;179605898;179605897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-28
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.4454
• 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/S	rs770837770	-0.565	0.001	N	0.245	0.103	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.30736E-04	None	0	0	0
T/S	rs770837770	-0.565	0.001	N	0.245	0.103	None	gnomAD-4.0.0	1.59215E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85789E-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	0.0863	likely_benign	0.0807	benign	-0.681	Destabilizing	None	N	0.231	neutral	N	0.517848947	None	None	I
T/C	0.4167	ambiguous	0.3887	ambiguous	-0.301	Destabilizing	0.667	D	0.589	neutral	None	None	None	None	I
T/D	0.3642	ambiguous	0.3482	ambiguous	0.269	Stabilizing	0.22	N	0.512	neutral	None	None	None	None	I
T/E	0.2823	likely_benign	0.2894	benign	0.247	Stabilizing	0.22	N	0.53	neutral	None	None	None	None	I
T/F	0.1931	likely_benign	0.2033	benign	-0.897	Destabilizing	0.497	N	0.608	neutral	None	None	None	None	I
T/G	0.3049	likely_benign	0.2847	benign	-0.893	Destabilizing	0.055	N	0.508	neutral	None	None	None	None	I
T/H	0.2334	likely_benign	0.2343	benign	-1.048	Destabilizing	0.667	D	0.584	neutral	None	None	None	None	I
T/I	0.1448	likely_benign	0.1415	benign	-0.217	Destabilizing	0.001	N	0.405	neutral	N	0.51385975	None	None	I
T/K	0.1977	likely_benign	0.1997	benign	-0.475	Destabilizing	0.124	N	0.529	neutral	None	None	None	None	I
T/L	0.1081	likely_benign	0.1084	benign	-0.217	Destabilizing	0.02	N	0.481	neutral	None	None	None	None	I
T/M	0.1127	likely_benign	0.1224	benign	-0.08	Destabilizing	0.497	N	0.595	neutral	None	None	None	None	I
T/N	0.1308	likely_benign	0.1273	benign	-0.289	Destabilizing	0.096	N	0.474	neutral	N	0.517973661	None	None	I
T/P	0.2056	likely_benign	0.1711	benign	-0.34	Destabilizing	0.001	N	0.426	neutral	D	0.64179754	None	None	I
T/Q	0.2331	likely_benign	0.2449	benign	-0.424	Destabilizing	0.497	N	0.639	neutral	None	None	None	None	I
T/R	0.1436	likely_benign	0.1503	benign	-0.235	Destabilizing	0.497	N	0.631	neutral	None	None	None	None	I
T/S	0.1089	likely_benign	0.1103	benign	-0.592	Destabilizing	0.001	N	0.245	neutral	N	0.440416847	None	None	I
T/V	0.1394	likely_benign	0.1327	benign	-0.34	Destabilizing	0.02	N	0.453	neutral	None	None	None	None	I
T/W	0.581	likely_pathogenic	0.5672	pathogenic	-0.864	Destabilizing	0.958	D	0.62	neutral	None	None	None	None	I
T/Y	0.2462	likely_benign	0.2401	benign	-0.619	Destabilizing	0.667	D	0.599	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.