TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24802	74629;74630;74631	chr2:178571728;178571727;178571726	chr2:179436455;179436454;179436453
N2AB	23161	69706;69707;69708	chr2:178571728;178571727;178571726	chr2:179436455;179436454;179436453
N2A	22234	66925;66926;66927	chr2:178571728;178571727;178571726	chr2:179436455;179436454;179436453
N2B	15737	47434;47435;47436	chr2:178571728;178571727;178571726	chr2:179436455;179436454;179436453
Novex-1	15862	47809;47810;47811	chr2:178571728;178571727;178571726	chr2:179436455;179436454;179436453
Novex-2	15929	48010;48011;48012	chr2:178571728;178571727;178571726	chr2:179436455;179436454;179436453
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-133
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.5044
• 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
N/H	None	None	0.896	N	0.56	0.238	0.280987212366	gnomAD-4.0.0	1.5919E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85951E-06	0	0
N/Y	rs1178547441	-0.159	0.963	D	0.629	0.352	0.536942225882	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/Y	rs1178547441	-0.159	0.963	D	0.629	0.352	0.536942225882	gnomAD-4.0.0	1.5919E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43312E-05	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	0.1817	likely_benign	0.1709	benign	-0.887	Destabilizing	0.25	N	0.493	neutral	None	None	None	None	I
N/C	0.2147	likely_benign	0.2003	benign	-0.111	Destabilizing	0.992	D	0.593	neutral	None	None	None	None	I
N/D	0.113	likely_benign	0.1128	benign	-1.16	Destabilizing	0.549	D	0.467	neutral	N	0.489730054	None	None	I
N/E	0.2582	likely_benign	0.2551	benign	-1.022	Destabilizing	0.25	N	0.453	neutral	None	None	None	None	I
N/F	0.5017	ambiguous	0.4862	ambiguous	-0.511	Destabilizing	0.92	D	0.618	neutral	None	None	None	None	I
N/G	0.2319	likely_benign	0.2167	benign	-1.261	Destabilizing	0.25	N	0.451	neutral	None	None	None	None	I
N/H	0.0744	likely_benign	0.0726	benign	-0.974	Destabilizing	0.896	D	0.56	neutral	N	0.466815909	None	None	I
N/I	0.2193	likely_benign	0.209	benign	0.082	Stabilizing	0.896	D	0.623	neutral	N	0.50183256	None	None	I
N/K	0.209	likely_benign	0.207	benign	-0.39	Destabilizing	0.379	N	0.447	neutral	N	0.480262422	None	None	I
N/L	0.2215	likely_benign	0.2008	benign	0.082	Stabilizing	0.617	D	0.594	neutral	None	None	None	None	I
N/M	0.2747	likely_benign	0.2612	benign	0.551	Stabilizing	0.992	D	0.61	neutral	None	None	None	None	I
N/P	0.703	likely_pathogenic	0.7004	pathogenic	-0.211	Destabilizing	0.92	D	0.616	neutral	None	None	None	None	I
N/Q	0.2199	likely_benign	0.2168	benign	-1.043	Destabilizing	0.059	N	0.303	neutral	None	None	None	None	I
N/R	0.239	likely_benign	0.2316	benign	-0.465	Destabilizing	0.617	D	0.528	neutral	None	None	None	None	I
N/S	0.0739	likely_benign	0.0705	benign	-1.103	Destabilizing	0.007	N	0.155	neutral	N	0.45828964	None	None	I
N/T	0.0864	likely_benign	0.0805	benign	-0.776	Destabilizing	0.379	N	0.449	neutral	N	0.403860509	None	None	I
N/V	0.2154	likely_benign	0.2063	benign	-0.211	Destabilizing	0.85	D	0.61	neutral	None	None	None	None	I
N/W	0.693	likely_pathogenic	0.6841	pathogenic	-0.306	Destabilizing	0.992	D	0.597	neutral	None	None	None	None	I
N/Y	0.1619	likely_benign	0.1569	benign	-0.062	Destabilizing	0.963	D	0.629	neutral	D	0.523189267	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.