TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29484	88675;88676;88677	chr2:178555009;178555008;178555007	chr2:179419736;179419735;179419734
N2AB	27843	83752;83753;83754	chr2:178555009;178555008;178555007	chr2:179419736;179419735;179419734
N2A	26916	80971;80972;80973	chr2:178555009;178555008;178555007	chr2:179419736;179419735;179419734
N2B	20419	61480;61481;61482	chr2:178555009;178555008;178555007	chr2:179419736;179419735;179419734
Novex-1	20544	61855;61856;61857	chr2:178555009;178555008;178555007	chr2:179419736;179419735;179419734
Novex-2	20611	62056;62057;62058	chr2:178555009;178555008;178555007	chr2:179419736;179419735;179419734
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-146
• Domain position: 41
• Structural Position: 73
• Q(SASA): 0.2542
• 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
N/K	None	None	0.379	N	0.225	0.078	0.115124310173	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
N/S	None	None	0.002	N	0.113	0.115	0.0762999501168	gnomAD-4.0.0	2.05278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69839E-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
N/A	0.2928	likely_benign	0.2195	benign	-0.182	Destabilizing	0.25	N	0.311	neutral	None	None	None	None	N
N/C	0.3413	ambiguous	0.2658	benign	0.363	Stabilizing	0.992	D	0.383	neutral	None	None	None	None	N
N/D	0.1023	likely_benign	0.0875	benign	0.137	Stabilizing	0.334	N	0.255	neutral	N	0.420631676	None	None	N
N/E	0.5163	ambiguous	0.3932	ambiguous	0.084	Stabilizing	0.617	D	0.219	neutral	None	None	None	None	N
N/F	0.7603	likely_pathogenic	0.6537	pathogenic	-0.685	Destabilizing	0.92	D	0.4	neutral	None	None	None	None	N
N/G	0.2124	likely_benign	0.187	benign	-0.314	Destabilizing	0.002	N	0.152	neutral	None	None	None	None	N
N/H	0.168	likely_benign	0.1373	benign	-0.391	Destabilizing	0.896	D	0.323	neutral	N	0.491995916	None	None	N
N/I	0.5252	ambiguous	0.3929	ambiguous	0.071	Stabilizing	0.81	D	0.431	neutral	N	0.456301225	None	None	N
N/K	0.4483	ambiguous	0.3301	benign	0.157	Stabilizing	0.379	N	0.225	neutral	N	0.472100646	None	None	N
N/L	0.3941	ambiguous	0.3222	benign	0.071	Stabilizing	0.617	D	0.382	neutral	None	None	None	None	N
N/M	0.5071	ambiguous	0.405	ambiguous	0.322	Stabilizing	0.992	D	0.338	neutral	None	None	None	None	N
N/P	0.7562	likely_pathogenic	0.6469	pathogenic	0.012	Stabilizing	0.92	D	0.411	neutral	None	None	None	None	N
N/Q	0.5113	ambiguous	0.4042	ambiguous	-0.229	Destabilizing	0.85	D	0.331	neutral	None	None	None	None	N
N/R	0.495	ambiguous	0.3686	ambiguous	0.2	Stabilizing	0.617	D	0.325	neutral	None	None	None	None	N
N/S	0.0722	likely_benign	0.0675	benign	0.01	Stabilizing	0.002	N	0.113	neutral	N	0.375261959	None	None	N
N/T	0.1204	likely_benign	0.1029	benign	0.083	Stabilizing	0.016	N	0.179	neutral	N	0.438257431	None	None	N
N/V	0.4492	ambiguous	0.3398	benign	0.012	Stabilizing	0.617	D	0.42	neutral	None	None	None	None	N
N/W	0.888	likely_pathogenic	0.8127	pathogenic	-0.754	Destabilizing	0.992	D	0.425	neutral	None	None	None	None	N
N/Y	0.3552	ambiguous	0.2619	benign	-0.453	Destabilizing	0.963	D	0.359	neutral	N	0.456301225	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.