TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33407	100444;100445;100446	chr2:178536528;178536527;178536526	chr2:179401255;179401254;179401253
N2AB	31766	95521;95522;95523	chr2:178536528;178536527;178536526	chr2:179401255;179401254;179401253
N2A	30839	92740;92741;92742	chr2:178536528;178536527;178536526	chr2:179401255;179401254;179401253
N2B	24342	73249;73250;73251	chr2:178536528;178536527;178536526	chr2:179401255;179401254;179401253
Novex-1	24467	73624;73625;73626	chr2:178536528;178536527;178536526	chr2:179401255;179401254;179401253
Novex-2	24534	73825;73826;73827	chr2:178536528;178536527;178536526	chr2:179401255;179401254;179401253
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-131
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3125
• 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
D/H	rs771684833	-0.868	0.992	N	0.675	0.429	0.255777322467	gnomAD-2.1.1	5.59E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.14E-05	0
D/H	rs771684833	-0.868	0.992	N	0.675	0.429	0.255777322467	gnomAD-4.0.0	5.08812E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.51994E-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	0.397	ambiguous	0.4053	ambiguous	-0.483	Destabilizing	0.698	D	0.631	neutral	N	0.482030755	None	None	N
D/C	0.864	likely_pathogenic	0.8634	pathogenic	-0.059	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
D/E	0.2322	likely_benign	0.1977	benign	-0.697	Destabilizing	0.014	N	0.302	neutral	N	0.487062604	None	None	N
D/F	0.7809	likely_pathogenic	0.7766	pathogenic	-0.673	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
D/G	0.3082	likely_benign	0.3453	ambiguous	-0.746	Destabilizing	0.822	D	0.564	neutral	N	0.47494041	None	None	N
D/H	0.5598	ambiguous	0.5767	pathogenic	-1.011	Destabilizing	0.992	D	0.675	neutral	N	0.515057282	None	None	N
D/I	0.6931	likely_pathogenic	0.7123	pathogenic	0.182	Stabilizing	0.978	D	0.766	deleterious	None	None	None	None	N
D/K	0.6891	likely_pathogenic	0.7209	pathogenic	-0.163	Destabilizing	0.754	D	0.617	neutral	None	None	None	None	N
D/L	0.6763	likely_pathogenic	0.6817	pathogenic	0.182	Stabilizing	0.956	D	0.763	deleterious	None	None	None	None	N
D/M	0.8246	likely_pathogenic	0.8072	pathogenic	0.668	Stabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
D/N	0.1357	likely_benign	0.1295	benign	-0.411	Destabilizing	0.126	N	0.299	neutral	N	0.454814112	None	None	N
D/P	0.9799	likely_pathogenic	0.9858	pathogenic	-0.016	Destabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	N
D/Q	0.5847	likely_pathogenic	0.5932	pathogenic	-0.367	Destabilizing	0.915	D	0.661	neutral	None	None	None	None	N
D/R	0.7604	likely_pathogenic	0.7901	pathogenic	-0.216	Destabilizing	0.956	D	0.73	prob.delet.	None	None	None	None	N
D/S	0.2398	likely_benign	0.2408	benign	-0.619	Destabilizing	0.754	D	0.508	neutral	None	None	None	None	N
D/T	0.3348	likely_benign	0.3282	benign	-0.408	Destabilizing	0.956	D	0.635	neutral	None	None	None	None	N
D/V	0.502	ambiguous	0.5244	ambiguous	-0.016	Destabilizing	0.942	D	0.764	deleterious	N	0.505161439	None	None	N
D/W	0.9599	likely_pathogenic	0.9624	pathogenic	-0.647	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
D/Y	0.3721	ambiguous	0.4015	ambiguous	-0.465	Destabilizing	0.997	D	0.76	deleterious	N	0.486803695	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.