TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25048	75367;75368;75369	chr2:178570990;178570989;178570988	chr2:179435717;179435716;179435715
N2AB	23407	70444;70445;70446	chr2:178570990;178570989;178570988	chr2:179435717;179435716;179435715
N2A	22480	67663;67664;67665	chr2:178570990;178570989;178570988	chr2:179435717;179435716;179435715
N2B	15983	48172;48173;48174	chr2:178570990;178570989;178570988	chr2:179435717;179435716;179435715
Novex-1	16108	48547;48548;48549	chr2:178570990;178570989;178570988	chr2:179435717;179435716;179435715
Novex-2	16175	48748;48749;48750	chr2:178570990;178570989;178570988	chr2:179435717;179435716;179435715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-70
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3827
• 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
L/S	rs774327169	-1.767	0.997	N	0.656	0.444	0.683575195277	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/S	rs774327169	-1.767	0.997	N	0.656	0.444	0.683575195277	gnomAD-4.0.0	6.15904E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09671E-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
L/A	0.6306	likely_pathogenic	0.61	pathogenic	-2.021	Highly Destabilizing	0.992	D	0.527	neutral	None	None	None	None	N
L/C	0.7618	likely_pathogenic	0.7178	pathogenic	-1.076	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
L/D	0.9194	likely_pathogenic	0.9176	pathogenic	-1.745	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/E	0.7642	likely_pathogenic	0.7561	pathogenic	-1.708	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/F	0.3529	ambiguous	0.3361	benign	-1.348	Destabilizing	0.998	D	0.591	neutral	N	0.472636232	None	None	N
L/G	0.8086	likely_pathogenic	0.8046	pathogenic	-2.376	Highly Destabilizing	0.269	N	0.511	neutral	None	None	None	None	N
L/H	0.5894	likely_pathogenic	0.571	pathogenic	-1.584	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
L/I	0.1429	likely_benign	0.1317	benign	-1.088	Destabilizing	0.978	D	0.481	neutral	N	0.503608137	None	None	N
L/K	0.6804	likely_pathogenic	0.6913	pathogenic	-1.457	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
L/M	0.199	likely_benign	0.1859	benign	-0.801	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	N
L/N	0.6822	likely_pathogenic	0.68	pathogenic	-1.292	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
L/P	0.8728	likely_pathogenic	0.8701	pathogenic	-1.372	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/Q	0.4905	ambiguous	0.4707	ambiguous	-1.465	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
L/R	0.6159	likely_pathogenic	0.6151	pathogenic	-0.815	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/S	0.7131	likely_pathogenic	0.7015	pathogenic	-1.882	Destabilizing	0.997	D	0.656	neutral	N	0.4663779	None	None	N
L/T	0.6026	likely_pathogenic	0.5843	pathogenic	-1.742	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	N
L/V	0.2086	likely_benign	0.182	benign	-1.372	Destabilizing	0.543	D	0.289	neutral	N	0.439826017	None	None	N
L/W	0.5384	ambiguous	0.5117	ambiguous	-1.479	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
L/Y	0.5766	likely_pathogenic	0.5502	ambiguous	-1.279	Destabilizing	1.0	D	0.635	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.