TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4769	14530;14531;14532	chr2:178738148;178738147;178738146	chr2:179602875;179602874;179602873
N2AB	4452	13579;13580;13581	chr2:178738148;178738147;178738146	chr2:179602875;179602874;179602873
N2A	3525	10798;10799;10800	chr2:178738148;178738147;178738146	chr2:179602875;179602874;179602873
N2B	4406	13441;13442;13443	chr2:178738148;178738147;178738146	chr2:179602875;179602874;179602873
Novex-1	4531	13816;13817;13818	chr2:178738148;178738147;178738146	chr2:179602875;179602874;179602873
Novex-2	4598	14017;14018;14019	chr2:178738148;178738147;178738146	chr2:179602875;179602874;179602873
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-30
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.682
• 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
E/G	None	None	1.0	D	0.749	0.587	0.552451585512	gnomAD-4.0.0	1.59132E-06	None	None	None	None	I	None	0	0	None	0	2.77454E-05	None	0	0	0	0	0
E/K	rs566108422	0.602	1.0	N	0.639	0.315	None	gnomAD-2.1.1	4.02E-05	None	None	None	None	I	None	2.58365E-04	5.8E-05	None	0	0	None	3.27E-05	None	0	1.78E-05	1.65782E-04
E/K	rs566108422	0.602	1.0	N	0.639	0.315	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	1.20633E-04	0	0	0	0	None	0	0	0	0	0
E/K	rs566108422	0.602	1.0	N	0.639	0.315	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs566108422	0.602	1.0	N	0.639	0.315	None	gnomAD-4.0.0	1.4252E-05	None	None	None	None	I	None	1.0661E-04	4.99833E-05	None	0	2.22955E-05	None	0	0	7.62857E-06	1.09796E-05	1.60061E-05
E/V	rs763092484	-0.007	1.0	N	0.779	0.498	0.558850992237	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	1.93748E-04	0	None	0	0	None	0	None	0	0	0
E/V	rs763092484	-0.007	1.0	N	0.779	0.498	0.558850992237	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/V	rs763092484	-0.007	1.0	N	0.779	0.498	0.558850992237	gnomAD-4.0.0	7.68647E-06	None	None	None	None	I	None	1.01464E-04	0	None	0	0	None	0	0	0	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
E/A	0.2452	likely_benign	0.3423	ambiguous	-0.647	Destabilizing	0.999	D	0.717	prob.delet.	D	0.550788561	None	None	I
E/C	0.9477	likely_pathogenic	0.9663	pathogenic	0.007	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/D	0.1888	likely_benign	0.2463	benign	-0.492	Destabilizing	0.999	D	0.556	neutral	N	0.511545165	None	None	I
E/F	0.8527	likely_pathogenic	0.9024	pathogenic	-0.487	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
E/G	0.3829	ambiguous	0.528	ambiguous	-0.883	Destabilizing	1.0	D	0.749	deleterious	D	0.701128233	None	None	I
E/H	0.6786	likely_pathogenic	0.7829	pathogenic	-0.518	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
E/I	0.4191	ambiguous	0.4853	ambiguous	-0.043	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/K	0.2462	likely_benign	0.3555	ambiguous	0.254	Stabilizing	1.0	D	0.639	neutral	N	0.506356399	None	None	I
E/L	0.5228	ambiguous	0.6204	pathogenic	-0.043	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/M	0.5554	ambiguous	0.6497	pathogenic	0.291	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
E/N	0.3504	ambiguous	0.4715	ambiguous	-0.124	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
E/P	0.7753	likely_pathogenic	0.8252	pathogenic	-0.224	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/Q	0.2111	likely_benign	0.2851	benign	-0.084	Destabilizing	1.0	D	0.65	neutral	N	0.506294339	None	None	I
E/R	0.4342	ambiguous	0.551	ambiguous	0.36	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/S	0.3109	likely_benign	0.4304	ambiguous	-0.303	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
E/T	0.299	likely_benign	0.3993	ambiguous	-0.103	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/V	0.2672	likely_benign	0.3308	benign	-0.224	Destabilizing	1.0	D	0.779	deleterious	N	0.509202351	None	None	I
E/W	0.9557	likely_pathogenic	0.9742	pathogenic	-0.278	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/Y	0.7783	likely_pathogenic	0.8549	pathogenic	-0.221	Destabilizing	1.0	D	0.761	deleterious	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.