TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9716	29371;29372;29373	chr2:178706728;178706727;178706726	chr2:179571455;179571454;179571453
N2AB	9399	28420;28421;28422	chr2:178706728;178706727;178706726	chr2:179571455;179571454;179571453
N2A	8472	25639;25640;25641	chr2:178706728;178706727;178706726	chr2:179571455;179571454;179571453
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-83
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4045
• 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/I	rs368642940	0.247	1.0	None	0.742	0.315	0.321672782286	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.76E-05	None	0	0	0
T/I	rs368642940	0.247	1.0	None	0.742	0.315	0.321672782286	gnomAD-4.0.0	1.16751E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.11633E-06	5.8782E-05	4.99085E-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
T/A	0.1973	likely_benign	0.1276	benign	-0.808	Destabilizing	0.996	D	0.525	neutral	None	None	None	None	N
T/C	0.7025	likely_pathogenic	0.5719	pathogenic	-0.575	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
T/D	0.8609	likely_pathogenic	0.6837	pathogenic	-0.033	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
T/E	0.6749	likely_pathogenic	0.5237	ambiguous	0.055	Stabilizing	0.997	D	0.644	neutral	None	None	None	None	N
T/F	0.5738	likely_pathogenic	0.3449	ambiguous	-0.771	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/G	0.7329	likely_pathogenic	0.5269	ambiguous	-1.129	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/H	0.5891	likely_pathogenic	0.3934	ambiguous	-1.185	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/I	0.1788	likely_benign	0.1342	benign	-0.023	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
T/K	0.5099	ambiguous	0.3335	benign	-0.416	Destabilizing	0.91	D	0.389	neutral	None	None	None	None	N
T/L	0.2128	likely_benign	0.1299	benign	-0.023	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
T/M	0.176	likely_benign	0.1264	benign	-0.089	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
T/N	0.4134	ambiguous	0.2345	benign	-0.689	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
T/P	0.8604	likely_pathogenic	0.616	pathogenic	-0.252	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/Q	0.5102	ambiguous	0.3601	ambiguous	-0.623	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
T/R	0.4267	ambiguous	0.2446	benign	-0.368	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
T/S	0.2924	likely_benign	0.1814	benign	-1.028	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	N
T/V	0.151	likely_benign	0.1242	benign	-0.252	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	N
T/W	0.892	likely_pathogenic	0.7603	pathogenic	-0.788	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
T/Y	0.6331	likely_pathogenic	0.4285	ambiguous	-0.47	Destabilizing	1.0	D	0.752	deleterious	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.