TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6395	19408;19409;19410	chr2:178728743;178728742;178728741	chr2:179593470;179593469;179593468
N2AB	6078	18457;18458;18459	chr2:178728743;178728742;178728741	chr2:179593470;179593469;179593468
N2A	5151	15676;15677;15678	chr2:178728743;178728742;178728741	chr2:179593470;179593469;179593468
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-48
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5653
• 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/G	None	None	0.27	N	0.323	0.172	0.225902525712	gnomAD-4.0.0	6.87558E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04225E-07	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	0.1962	likely_benign	0.14	benign	-0.264	Destabilizing	0.27	N	0.298	neutral	N	0.453961255	None	None	N
D/C	0.7965	likely_pathogenic	0.6029	pathogenic	-0.129	Destabilizing	0.995	D	0.291	neutral	None	None	None	None	N
D/E	0.1875	likely_benign	0.1481	benign	-0.34	Destabilizing	0.27	N	0.255	neutral	N	0.423136916	None	None	N
D/F	0.612	likely_pathogenic	0.4945	ambiguous	0.015	Stabilizing	0.981	D	0.325	neutral	None	None	None	None	N
D/G	0.3291	likely_benign	0.2472	benign	-0.504	Destabilizing	0.27	N	0.323	neutral	N	0.502485921	None	None	N
D/H	0.3447	ambiguous	0.2396	benign	0.164	Stabilizing	0.927	D	0.316	neutral	N	0.487575184	None	None	N
D/I	0.3629	ambiguous	0.2574	benign	0.332	Stabilizing	0.944	D	0.381	neutral	None	None	None	None	N
D/K	0.4425	ambiguous	0.3217	benign	0.244	Stabilizing	0.001	N	0.137	neutral	None	None	None	None	N
D/L	0.3982	ambiguous	0.2923	benign	0.332	Stabilizing	0.704	D	0.378	neutral	None	None	None	None	N
D/M	0.5974	likely_pathogenic	0.4721	ambiguous	0.356	Stabilizing	0.981	D	0.303	neutral	None	None	None	None	N
D/N	0.1174	likely_benign	0.0956	benign	-0.223	Destabilizing	0.002	N	0.094	neutral	N	0.415232296	None	None	N
D/P	0.7887	likely_pathogenic	0.6758	pathogenic	0.157	Stabilizing	0.828	D	0.351	neutral	None	None	None	None	N
D/Q	0.3976	ambiguous	0.2953	benign	-0.15	Destabilizing	0.704	D	0.182	neutral	None	None	None	None	N
D/R	0.4908	ambiguous	0.3635	ambiguous	0.483	Stabilizing	0.543	D	0.317	neutral	None	None	None	None	N
D/S	0.1466	likely_benign	0.1183	benign	-0.322	Destabilizing	0.013	N	0.087	neutral	None	None	None	None	N
D/T	0.2399	likely_benign	0.1766	benign	-0.127	Destabilizing	0.329	N	0.285	neutral	None	None	None	None	N
D/V	0.2096	likely_benign	0.146	benign	0.157	Stabilizing	0.642	D	0.389	neutral	N	0.445475058	None	None	N
D/W	0.8934	likely_pathogenic	0.8304	pathogenic	0.195	Stabilizing	0.995	D	0.363	neutral	None	None	None	None	N
D/Y	0.2701	likely_benign	0.198	benign	0.266	Stabilizing	0.975	D	0.328	neutral	N	0.475627394	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.