TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24966	75121;75122;75123	chr2:178571236;178571235;178571234	chr2:179435963;179435962;179435961
N2AB	23325	70198;70199;70200	chr2:178571236;178571235;178571234	chr2:179435963;179435962;179435961
N2A	22398	67417;67418;67419	chr2:178571236;178571235;178571234	chr2:179435963;179435962;179435961
N2B	15901	47926;47927;47928	chr2:178571236;178571235;178571234	chr2:179435963;179435962;179435961
Novex-1	16026	48301;48302;48303	chr2:178571236;178571235;178571234	chr2:179435963;179435962;179435961
Novex-2	16093	48502;48503;48504	chr2:178571236;178571235;178571234	chr2:179435963;179435962;179435961
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: Fn3-69
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.3065
• 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/N	None	None	0.204	N	0.385	0.25	0.239305524855	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1272	likely_benign	0.1223	benign	-0.86	Destabilizing	0.892	D	0.453	neutral	N	0.473334249	None	None	N
T/C	0.2787	likely_benign	0.2687	benign	-0.537	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
T/D	0.5671	likely_pathogenic	0.5642	pathogenic	-0.989	Destabilizing	0.95	D	0.581	neutral	None	None	None	None	N
T/E	0.4558	ambiguous	0.4382	ambiguous	-0.821	Destabilizing	0.975	D	0.579	neutral	None	None	None	None	N
T/F	0.494	ambiguous	0.4771	ambiguous	-0.57	Destabilizing	0.975	D	0.701	prob.neutral	None	None	None	None	N
T/G	0.2525	likely_benign	0.2432	benign	-1.257	Destabilizing	0.916	D	0.583	neutral	None	None	None	None	N
T/H	0.3521	ambiguous	0.3387	benign	-1.356	Destabilizing	0.997	D	0.697	prob.neutral	None	None	None	None	N
T/I	0.3302	likely_benign	0.3128	benign	0.167	Stabilizing	0.935	D	0.587	neutral	N	0.507834465	None	None	N
T/K	0.177	likely_benign	0.1669	benign	-0.532	Destabilizing	0.975	D	0.582	neutral	None	None	None	None	N
T/L	0.0876	likely_benign	0.08	benign	0.167	Stabilizing	0.033	N	0.373	neutral	None	None	None	None	N
T/M	0.0955	likely_benign	0.0902	benign	0.104	Stabilizing	0.993	D	0.657	neutral	None	None	None	None	N
T/N	0.1018	likely_benign	0.1066	benign	-1.072	Destabilizing	0.204	N	0.385	neutral	N	0.484650874	None	None	N
T/P	0.1434	likely_benign	0.1479	benign	-0.143	Destabilizing	0.994	D	0.637	neutral	N	0.487234995	None	None	N
T/Q	0.2272	likely_benign	0.2101	benign	-0.871	Destabilizing	0.987	D	0.655	neutral	None	None	None	None	N
T/R	0.1393	likely_benign	0.1347	benign	-0.654	Destabilizing	0.987	D	0.637	neutral	None	None	None	None	N
T/S	0.1747	likely_benign	0.1669	benign	-1.309	Destabilizing	0.892	D	0.457	neutral	N	0.490171056	None	None	N
T/V	0.1991	likely_benign	0.1856	benign	-0.143	Destabilizing	0.845	D	0.438	neutral	None	None	None	None	N
T/W	0.7458	likely_pathogenic	0.7255	pathogenic	-0.752	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
T/Y	0.423	ambiguous	0.4054	ambiguous	-0.366	Destabilizing	0.987	D	0.703	prob.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.