TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19168	57727;57728;57729	chr2:178597580;178597579;178597578	chr2:179462307;179462306;179462305
N2AB	17527	52804;52805;52806	chr2:178597580;178597579;178597578	chr2:179462307;179462306;179462305
N2A	16600	50023;50024;50025	chr2:178597580;178597579;178597578	chr2:179462307;179462306;179462305
N2B	10103	30532;30533;30534	chr2:178597580;178597579;178597578	chr2:179462307;179462306;179462305
Novex-1	10228	30907;30908;30909	chr2:178597580;178597579;178597578	chr2:179462307;179462306;179462305
Novex-2	10295	31108;31109;31110	chr2:178597580;178597579;178597578	chr2:179462307;179462306;179462305
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-117
• Domain position: 74
• Structural Position: 162
• Q(SASA): 0.8458
• 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/D	None	None	None	N	0.285	0.099	0.168933306366	gnomAD-4.0.0	1.59371E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43563E-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
E/A	0.0519	likely_benign	0.0698	benign	-0.028	Destabilizing	None	N	0.204	neutral	N	0.448192863	None	None	I
E/C	0.6078	likely_pathogenic	0.7051	pathogenic	-0.024	Destabilizing	0.824	D	0.411	neutral	None	None	None	None	I
E/D	0.0873	likely_benign	0.0922	benign	-0.274	Destabilizing	None	N	0.285	neutral	N	0.467298699	None	None	I
E/F	0.4802	ambiguous	0.6068	pathogenic	-0.108	Destabilizing	0.555	D	0.415	neutral	None	None	None	None	I
E/G	0.0901	likely_benign	0.1124	benign	-0.146	Destabilizing	0.027	N	0.414	neutral	N	0.510396115	None	None	I
E/H	0.2708	likely_benign	0.3287	benign	0.411	Stabilizing	0.791	D	0.383	neutral	None	None	None	None	I
E/I	0.149	likely_benign	0.2001	benign	0.223	Stabilizing	0.38	N	0.433	neutral	None	None	None	None	I
E/K	0.0898	likely_benign	0.1004	benign	0.511	Stabilizing	0.117	N	0.423	neutral	N	0.458639143	None	None	I
E/L	0.1706	likely_benign	0.2296	benign	0.223	Stabilizing	0.081	N	0.442	neutral	None	None	None	None	I
E/M	0.2102	likely_benign	0.2806	benign	0.095	Stabilizing	0.824	D	0.439	neutral	None	None	None	None	I
E/N	0.1331	likely_benign	0.1583	benign	0.298	Stabilizing	0.081	N	0.367	neutral	None	None	None	None	I
E/P	0.1697	likely_benign	0.245	benign	0.157	Stabilizing	0.38	N	0.409	neutral	None	None	None	None	I
E/Q	0.0976	likely_benign	0.1148	benign	0.302	Stabilizing	0.211	N	0.401	neutral	N	0.510222757	None	None	I
E/R	0.1526	likely_benign	0.1877	benign	0.684	Stabilizing	0.38	N	0.365	neutral	None	None	None	None	I
E/S	0.0846	likely_benign	0.1062	benign	0.159	Stabilizing	0.035	N	0.389	neutral	None	None	None	None	I
E/T	0.0838	likely_benign	0.1128	benign	0.261	Stabilizing	0.081	N	0.451	neutral	None	None	None	None	I
E/V	0.0991	likely_benign	0.1258	benign	0.157	Stabilizing	0.062	N	0.46	neutral	N	0.479401205	None	None	I
E/W	0.7485	likely_pathogenic	0.8293	pathogenic	-0.068	Destabilizing	0.935	D	0.489	neutral	None	None	None	None	I
E/Y	0.3914	ambiguous	0.4926	ambiguous	0.119	Stabilizing	0.555	D	0.442	neutral	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.