TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25236	75931;75932;75933	chr2:178570426;178570425;178570424	chr2:179435153;179435152;179435151
N2AB	23595	71008;71009;71010	chr2:178570426;178570425;178570424	chr2:179435153;179435152;179435151
N2A	22668	68227;68228;68229	chr2:178570426;178570425;178570424	chr2:179435153;179435152;179435151
N2B	16171	48736;48737;48738	chr2:178570426;178570425;178570424	chr2:179435153;179435152;179435151
Novex-1	16296	49111;49112;49113	chr2:178570426;178570425;178570424	chr2:179435153;179435152;179435151
Novex-2	16363	49312;49313;49314	chr2:178570426;178570425;178570424	chr2:179435153;179435152;179435151
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-71
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.9029
• 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
D/E	None	None	0.067	N	0.201	0.044	0.0297737177859	gnomAD-4.0.0	6.84467E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99612E-07	0	0
D/N	rs1707754880	None	0.988	N	0.666	0.245	0.222439326576	gnomAD-4.0.0	3.18544E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71961E-06	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
D/A	0.105	likely_benign	0.1243	benign	-0.22	Destabilizing	0.958	D	0.582	neutral	N	0.413199563	None	None	I
D/C	0.4697	ambiguous	0.5431	ambiguous	0.124	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
D/E	0.1145	likely_benign	0.124	benign	-0.246	Destabilizing	0.067	N	0.201	neutral	N	0.388223761	None	None	I
D/F	0.5719	likely_pathogenic	0.6157	pathogenic	-0.232	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/G	0.1449	likely_benign	0.1587	benign	-0.4	Destabilizing	0.958	D	0.61	neutral	N	0.449891082	None	None	I
D/H	0.2111	likely_benign	0.2405	benign	-0.089	Destabilizing	0.998	D	0.635	neutral	N	0.494604651	None	None	I
D/I	0.281	likely_benign	0.3205	benign	0.2	Stabilizing	0.995	D	0.663	neutral	None	None	None	None	I
D/K	0.218	likely_benign	0.26	benign	0.411	Stabilizing	0.982	D	0.629	neutral	None	None	None	None	I
D/L	0.3009	likely_benign	0.347	ambiguous	0.2	Stabilizing	0.991	D	0.658	neutral	None	None	None	None	I
D/M	0.4727	ambiguous	0.5301	ambiguous	0.346	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	I
D/N	0.0828	likely_benign	0.0869	benign	0.143	Stabilizing	0.988	D	0.666	neutral	N	0.458702566	None	None	I
D/P	0.3061	likely_benign	0.3832	ambiguous	0.082	Stabilizing	0.995	D	0.66	neutral	None	None	None	None	I
D/Q	0.2317	likely_benign	0.2634	benign	0.171	Stabilizing	0.982	D	0.695	prob.neutral	None	None	None	None	I
D/R	0.291	likely_benign	0.335	benign	0.511	Stabilizing	0.991	D	0.667	neutral	None	None	None	None	I
D/S	0.0972	likely_benign	0.1018	benign	0.045	Stabilizing	0.968	D	0.598	neutral	None	None	None	None	I
D/T	0.164	likely_benign	0.1804	benign	0.187	Stabilizing	0.991	D	0.624	neutral	None	None	None	None	I
D/V	0.1566	likely_benign	0.1836	benign	0.082	Stabilizing	0.994	D	0.657	neutral	N	0.506744442	None	None	I
D/W	0.872	likely_pathogenic	0.8954	pathogenic	-0.129	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
D/Y	0.2334	likely_benign	0.2608	benign	None	Stabilizing	0.999	D	0.642	neutral	N	0.507611234	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.