TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30909	92950;92951;92952	chr2:178548901;178548900;178548899	chr2:179413628;179413627;179413626
N2AB	29268	88027;88028;88029	chr2:178548901;178548900;178548899	chr2:179413628;179413627;179413626
N2A	28341	85246;85247;85248	chr2:178548901;178548900;178548899	chr2:179413628;179413627;179413626
N2B	21844	65755;65756;65757	chr2:178548901;178548900;178548899	chr2:179413628;179413627;179413626
Novex-1	21969	66130;66131;66132	chr2:178548901;178548900;178548899	chr2:179413628;179413627;179413626
Novex-2	22036	66331;66332;66333	chr2:178548901;178548900;178548899	chr2:179413628;179413627;179413626
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: Fn3-113
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.2551
• 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
E/K	rs1486624506	None	0.935	N	0.509	0.22	0.241664281697	gnomAD-4.0.0	6.84199E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65662E-05
E/Q	rs1486624506	-0.82	0.994	N	0.508	0.171	0.167679373172	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/Q	rs1486624506	-0.82	0.994	N	0.508	0.171	0.167679373172	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/Q	rs1486624506	-0.82	0.994	N	0.508	0.171	0.167679373172	gnomAD-4.0.0	3.09835E-06	None	None	None	None	N	None	0	8.33444E-05	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	0.162	likely_benign	0.1558	benign	-0.87	Destabilizing	0.78	D	0.527	neutral	N	0.480778844	None	None	N
E/C	0.8063	likely_pathogenic	0.7965	pathogenic	-0.456	Destabilizing	0.999	D	0.659	prob.neutral	None	None	None	None	N
E/D	0.1367	likely_benign	0.1419	benign	-0.978	Destabilizing	0.978	D	0.532	neutral	N	0.458902062	None	None	N
E/F	0.6814	likely_pathogenic	0.6736	pathogenic	-0.174	Destabilizing	0.971	D	0.683	prob.neutral	None	None	None	None	N
E/G	0.2403	likely_benign	0.2359	benign	-1.236	Destabilizing	0.981	D	0.599	neutral	N	0.513968698	None	None	N
E/H	0.465	ambiguous	0.4513	ambiguous	-0.318	Destabilizing	0.999	D	0.508	neutral	None	None	None	None	N
E/I	0.2933	likely_benign	0.2861	benign	0.129	Stabilizing	0.825	D	0.644	neutral	None	None	None	None	N
E/K	0.1869	likely_benign	0.181	benign	-0.458	Destabilizing	0.935	D	0.509	neutral	N	0.488936968	None	None	N
E/L	0.3215	likely_benign	0.3146	benign	0.129	Stabilizing	0.825	D	0.619	neutral	None	None	None	None	N
E/M	0.3643	ambiguous	0.359	ambiguous	0.494	Stabilizing	0.996	D	0.623	neutral	None	None	None	None	N
E/N	0.2786	likely_benign	0.2779	benign	-1.028	Destabilizing	0.995	D	0.461	neutral	None	None	None	None	N
E/P	0.4746	ambiguous	0.4767	ambiguous	-0.183	Destabilizing	0.995	D	0.498	neutral	None	None	None	None	N
E/Q	0.1643	likely_benign	0.1596	benign	-0.885	Destabilizing	0.994	D	0.508	neutral	N	0.499519321	None	None	N
E/R	0.3238	likely_benign	0.3063	benign	-0.115	Destabilizing	0.985	D	0.467	neutral	None	None	None	None	N
E/S	0.2163	likely_benign	0.2115	benign	-1.315	Destabilizing	0.95	D	0.499	neutral	None	None	None	None	N
E/T	0.2069	likely_benign	0.1972	benign	-1.005	Destabilizing	0.904	D	0.531	neutral	None	None	None	None	N
E/V	0.1794	likely_benign	0.1758	benign	-0.183	Destabilizing	0.022	N	0.558	neutral	N	0.510891108	None	None	N
E/W	0.8909	likely_pathogenic	0.8877	pathogenic	0.152	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	N
E/Y	0.598	likely_pathogenic	0.5939	pathogenic	0.106	Stabilizing	0.985	D	0.655	prob.neutral	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.