TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31657	95194;95195;95196	chr2:178546362;178546361;178546360	chr2:179411089;179411088;179411087
N2AB	30016	90271;90272;90273	chr2:178546362;178546361;178546360	chr2:179411089;179411088;179411087
N2A	29089	87490;87491;87492	chr2:178546362;178546361;178546360	chr2:179411089;179411088;179411087
N2B	22592	67999;68000;68001	chr2:178546362;178546361;178546360	chr2:179411089;179411088;179411087
Novex-1	22717	68374;68375;68376	chr2:178546362;178546361;178546360	chr2:179411089;179411088;179411087
Novex-2	22784	68575;68576;68577	chr2:178546362;178546361;178546360	chr2:179411089;179411088;179411087
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: Ig-152
• Domain position: 37
• Structural Position: 69
• Q(SASA): 0.6573
• 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/E	rs781088841	-0.024	0.006	N	0.264	0.06	0.119812018005	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
D/E	rs781088841	-0.024	0.006	N	0.264	0.06	0.119812018005	gnomAD-4.0.0	3.42103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9948E-07	4.63736E-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
D/A	0.1242	likely_benign	0.1293	benign	-0.024	Destabilizing	0.698	D	0.53	neutral	N	0.483052011	None	None	N
D/C	0.49	ambiguous	0.5295	ambiguous	-0.136	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
D/E	0.112	likely_benign	0.1196	benign	-0.236	Destabilizing	0.006	N	0.264	neutral	N	0.43691429	None	None	N
D/F	0.4463	ambiguous	0.4715	ambiguous	0.131	Stabilizing	0.993	D	0.635	neutral	None	None	None	None	N
D/G	0.1415	likely_benign	0.15	benign	-0.224	Destabilizing	0.822	D	0.559	neutral	N	0.470528218	None	None	N
D/H	0.2236	likely_benign	0.2451	benign	0.484	Stabilizing	0.992	D	0.545	neutral	N	0.5217064	None	None	N
D/I	0.2069	likely_benign	0.2312	benign	0.451	Stabilizing	0.978	D	0.644	neutral	None	None	None	None	N
D/K	0.3044	likely_benign	0.3306	benign	0.327	Stabilizing	0.754	D	0.539	neutral	None	None	None	None	N
D/L	0.2241	likely_benign	0.2378	benign	0.451	Stabilizing	0.956	D	0.63	neutral	None	None	None	None	N
D/M	0.414	ambiguous	0.4556	ambiguous	0.294	Stabilizing	0.998	D	0.63	neutral	None	None	None	None	N
D/N	0.1089	likely_benign	0.1167	benign	-0.042	Destabilizing	0.822	D	0.523	neutral	N	0.452729104	None	None	N
D/P	0.444	ambiguous	0.4488	ambiguous	0.316	Stabilizing	0.978	D	0.555	neutral	None	None	None	None	N
D/Q	0.2198	likely_benign	0.2393	benign	0.025	Stabilizing	0.915	D	0.491	neutral	None	None	None	None	N
D/R	0.3188	likely_benign	0.3426	ambiguous	0.6	Stabilizing	0.956	D	0.582	neutral	None	None	None	None	N
D/S	0.1103	likely_benign	0.1168	benign	-0.143	Destabilizing	0.754	D	0.525	neutral	None	None	None	None	N
D/T	0.1755	likely_benign	0.1927	benign	0.021	Stabilizing	0.956	D	0.513	neutral	None	None	None	None	N
D/V	0.122	likely_benign	0.1339	benign	0.316	Stabilizing	0.942	D	0.619	neutral	N	0.446189921	None	None	N
D/W	0.8107	likely_pathogenic	0.8258	pathogenic	0.236	Stabilizing	0.998	D	0.645	neutral	None	None	None	None	N
D/Y	0.1897	likely_benign	0.2026	benign	0.368	Stabilizing	0.99	D	0.635	neutral	N	0.499330973	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.