TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25032	75319;75320;75321	chr2:178571038;178571037;178571036	chr2:179435765;179435764;179435763
N2AB	23391	70396;70397;70398	chr2:178571038;178571037;178571036	chr2:179435765;179435764;179435763
N2A	22464	67615;67616;67617	chr2:178571038;178571037;178571036	chr2:179435765;179435764;179435763
N2B	15967	48124;48125;48126	chr2:178571038;178571037;178571036	chr2:179435765;179435764;179435763
Novex-1	16092	48499;48500;48501	chr2:178571038;178571037;178571036	chr2:179435765;179435764;179435763
Novex-2	16159	48700;48701;48702	chr2:178571038;178571037;178571036	chr2:179435765;179435764;179435763
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-70
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4882
• 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
Y/C	None	None	0.997	N	0.691	0.252	0.28492961333	gnomAD-4.0.0	2.73904E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70065E-06	0	1.65804E-05
Y/S	None	None	0.125	N	0.394	0.216	0.260735089382	gnomAD-4.0.0	6.84761E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00218E-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
Y/A	0.6563	likely_pathogenic	0.6192	pathogenic	-1.011	Destabilizing	0.754	D	0.574	neutral	None	None	None	None	I
Y/C	0.2455	likely_benign	0.2186	benign	0.154	Stabilizing	0.997	D	0.691	prob.neutral	N	0.46955318	None	None	I
Y/D	0.4639	ambiguous	0.4631	ambiguous	0.75	Stabilizing	0.942	D	0.68	prob.neutral	N	0.464227737	None	None	I
Y/E	0.8103	likely_pathogenic	0.8018	pathogenic	0.733	Stabilizing	0.956	D	0.549	neutral	None	None	None	None	I
Y/F	0.1247	likely_benign	0.124	benign	-0.63	Destabilizing	0.014	N	0.289	neutral	N	0.479621264	None	None	I
Y/G	0.5318	ambiguous	0.4963	ambiguous	-1.224	Destabilizing	0.754	D	0.569	neutral	None	None	None	None	I
Y/H	0.2837	likely_benign	0.2794	benign	-0.089	Destabilizing	0.99	D	0.533	neutral	N	0.471887215	None	None	I
Y/I	0.7679	likely_pathogenic	0.7378	pathogenic	-0.457	Destabilizing	0.956	D	0.516	neutral	None	None	None	None	I
Y/K	0.7631	likely_pathogenic	0.7566	pathogenic	0.152	Stabilizing	0.956	D	0.56	neutral	None	None	None	None	I
Y/L	0.6913	likely_pathogenic	0.645	pathogenic	-0.457	Destabilizing	0.754	D	0.595	neutral	None	None	None	None	I
Y/M	0.7617	likely_pathogenic	0.7371	pathogenic	-0.066	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	I
Y/N	0.2056	likely_benign	0.2143	benign	0.104	Stabilizing	0.942	D	0.657	neutral	N	0.49516672	None	None	I
Y/P	0.9832	likely_pathogenic	0.9807	pathogenic	-0.623	Destabilizing	0.978	D	0.691	prob.neutral	None	None	None	None	I
Y/Q	0.7037	likely_pathogenic	0.6896	pathogenic	0.066	Stabilizing	0.956	D	0.572	neutral	None	None	None	None	I
Y/R	0.5499	ambiguous	0.5476	ambiguous	0.519	Stabilizing	0.956	D	0.661	neutral	None	None	None	None	I
Y/S	0.273	likely_benign	0.2657	benign	-0.411	Destabilizing	0.125	N	0.394	neutral	N	0.43979344	None	None	I
Y/T	0.5987	likely_pathogenic	0.5793	pathogenic	-0.335	Destabilizing	0.915	D	0.534	neutral	None	None	None	None	I
Y/V	0.6182	likely_pathogenic	0.5825	pathogenic	-0.623	Destabilizing	0.86	D	0.557	neutral	None	None	None	None	I
Y/W	0.4719	ambiguous	0.4486	ambiguous	-0.658	Destabilizing	0.998	D	0.532	neutral	None	None	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.