TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25492	76699;76700;76701	chr2:178569658;178569657;178569656	chr2:179434385;179434384;179434383
N2AB	23851	71776;71777;71778	chr2:178569658;178569657;178569656	chr2:179434385;179434384;179434383
N2A	22924	68995;68996;68997	chr2:178569658;178569657;178569656	chr2:179434385;179434384;179434383
N2B	16427	49504;49505;49506	chr2:178569658;178569657;178569656	chr2:179434385;179434384;179434383
Novex-1	16552	49879;49880;49881	chr2:178569658;178569657;178569656	chr2:179434385;179434384;179434383
Novex-2	16619	50080;50081;50082	chr2:178569658;178569657;178569656	chr2:179434385;179434384;179434383
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-73
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.4661
• 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
H/L	rs766094077	0.799	0.684	N	0.594	0.188	0.423360453849	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.68E-05	0	0
H/L	rs766094077	0.799	0.684	N	0.594	0.188	0.423360453849	gnomAD-4.0.0	1.59436E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86234E-06	0	0
H/P	rs766094077	None	0.007	N	0.503	0.267	0.139678290688	gnomAD-4.0.0	1.59436E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86234E-06	0	0
H/Q	None	None	0.939	N	0.558	0.198	0.128392430309	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
H/A	0.2306	likely_benign	0.2372	benign	0.139	Stabilizing	0.742	D	0.561	neutral	None	None	None	None	I
H/C	0.1713	likely_benign	0.1885	benign	1.007	Stabilizing	0.996	D	0.673	neutral	None	None	None	None	I
H/D	0.3405	ambiguous	0.367	ambiguous	None	Stabilizing	0.815	D	0.537	neutral	N	0.464806527	None	None	I
H/E	0.4192	ambiguous	0.4589	ambiguous	0.051	Stabilizing	0.742	D	0.471	neutral	None	None	None	None	I
H/F	0.3021	likely_benign	0.3315	benign	0.942	Stabilizing	0.984	D	0.613	neutral	None	None	None	None	I
H/G	0.3692	ambiguous	0.4008	ambiguous	-0.191	Destabilizing	0.742	D	0.556	neutral	None	None	None	None	I
H/I	0.4537	ambiguous	0.5033	ambiguous	1.012	Stabilizing	0.91	D	0.646	neutral	None	None	None	None	I
H/K	0.3488	ambiguous	0.3876	ambiguous	0.234	Stabilizing	0.742	D	0.531	neutral	None	None	None	None	I
H/L	0.2086	likely_benign	0.2329	benign	1.012	Stabilizing	0.684	D	0.594	neutral	N	0.476983604	None	None	I
H/M	0.5438	ambiguous	0.5806	pathogenic	0.866	Stabilizing	0.996	D	0.649	neutral	None	None	None	None	I
H/N	0.148	likely_benign	0.1629	benign	0.396	Stabilizing	0.815	D	0.517	neutral	N	0.464806527	None	None	I
H/P	0.0774	likely_benign	0.0871	benign	0.745	Stabilizing	0.007	N	0.503	neutral	N	0.324368991	None	None	I
H/Q	0.2553	likely_benign	0.2808	benign	0.563	Stabilizing	0.939	D	0.558	neutral	N	0.507999944	None	None	I
H/R	0.1685	likely_benign	0.1974	benign	-0.516	Destabilizing	0.939	D	0.531	neutral	N	0.478023754	None	None	I
H/S	0.2438	likely_benign	0.2583	benign	0.529	Stabilizing	0.59	D	0.497	neutral	None	None	None	None	I
H/T	0.3315	likely_benign	0.3575	ambiguous	0.673	Stabilizing	0.037	N	0.506	neutral	None	None	None	None	I
H/V	0.3509	ambiguous	0.3866	ambiguous	0.745	Stabilizing	0.742	D	0.605	neutral	None	None	None	None	I
H/W	0.4142	ambiguous	0.4435	ambiguous	0.967	Stabilizing	0.996	D	0.662	neutral	None	None	None	None	I
H/Y	0.0984	likely_benign	0.1071	benign	1.228	Stabilizing	0.979	D	0.567	neutral	N	0.420052886	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.