TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24947	75064;75065;75066	chr2:178571293;178571292;178571291	chr2:179436020;179436019;179436018
N2AB	23306	70141;70142;70143	chr2:178571293;178571292;178571291	chr2:179436020;179436019;179436018
N2A	22379	67360;67361;67362	chr2:178571293;178571292;178571291	chr2:179436020;179436019;179436018
N2B	15882	47869;47870;47871	chr2:178571293;178571292;178571291	chr2:179436020;179436019;179436018
Novex-1	16007	48244;48245;48246	chr2:178571293;178571292;178571291	chr2:179436020;179436019;179436018
Novex-2	16074	48445;48446;48447	chr2:178571293;178571292;178571291	chr2:179436020;179436019;179436018
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-69
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1197
• 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
R/C	rs744426	-1.929	0.999	D	0.749	0.301	None	gnomAD-2.1.1	1.71489E-01	None	None	None	None	N	None	7.1464E-02	1.45197E-01	None	1.66828E-01	4.28829E-01	None	2.52124E-01	None	1.51604E-01	1.44201E-01	1.58982E-01
R/C	rs744426	-1.929	0.999	D	0.749	0.301	None	gnomAD-3.1.2	1.40561E-01	None	None	None	None	N	None	7.52914E-02	1.26759E-01	4.66887E-01	1.68108E-01	4.39719E-01	None	1.6125E-01	1.13924E-01	1.44401E-01	2.54273E-01	1.25359E-01
R/C	rs744426	-1.929	0.999	D	0.749	0.301	None	1000 genomes	2.08067E-01	None	None	None	None	N	None	6.66E-02	1.455E-01	None	None	4.504E-01	1.372E-01	None	None	None	2.669E-01	None
R/C	rs744426	-1.929	0.999	D	0.749	0.301	None	gnomAD-4.0.0	1.52119E-01	None	None	None	None	N	None	7.33413E-02	1.40069E-01	None	1.6625E-01	4.33831E-01	None	1.52941E-01	1.26032E-01	1.38545E-01	2.49808E-01	1.60641E-01
R/H	rs765512476	-2.088	0.998	N	0.651	0.28	0.359963025489	gnomAD-2.1.1	3.93E-05	None	None	None	None	N	None	0	0	None	0	1.02891E-04	None	0	None	4E-05	5.49E-05	1.40528E-04
R/H	rs765512476	-2.088	0.998	N	0.651	0.28	0.359963025489	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	2.94E-05	0	0
R/H	rs765512476	-2.088	0.998	N	0.651	0.28	0.359963025489	gnomAD-4.0.0	7.43763E-06	None	None	None	None	N	None	0	0	None	0	4.46528E-05	None	3.1251E-05	0	6.78207E-06	0	0
R/S	None	None	0.055	N	0.379	0.177	0.231873229951	gnomAD-4.0.0	6.84331E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99601E-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
R/A	0.61	likely_pathogenic	0.6339	pathogenic	-2.208	Highly Destabilizing	0.525	D	0.497	neutral	None	None	None	None	N
R/C	0.1484	likely_benign	0.1443	benign	-2.058	Highly Destabilizing	0.999	D	0.749	deleterious	D	0.522537827	None	None	N
R/D	0.9616	likely_pathogenic	0.9585	pathogenic	-1.425	Destabilizing	0.842	D	0.654	neutral	None	None	None	None	N
R/E	0.6602	likely_pathogenic	0.6638	pathogenic	-1.168	Destabilizing	0.842	D	0.567	neutral	None	None	None	None	N
R/F	0.6668	likely_pathogenic	0.7065	pathogenic	-1.239	Destabilizing	0.949	D	0.733	prob.delet.	None	None	None	None	N
R/G	0.5002	ambiguous	0.5101	ambiguous	-2.585	Highly Destabilizing	0.837	D	0.644	neutral	N	0.480496591	None	None	N
R/H	0.181	likely_benign	0.1727	benign	-1.781	Destabilizing	0.998	D	0.651	neutral	N	0.509995391	None	None	N
R/I	0.4497	ambiguous	0.4957	ambiguous	-1.09	Destabilizing	0.728	D	0.698	prob.neutral	None	None	None	None	N
R/K	0.1235	likely_benign	0.1317	benign	-1.097	Destabilizing	0.688	D	0.515	neutral	None	None	None	None	N
R/L	0.4184	ambiguous	0.4556	ambiguous	-1.09	Destabilizing	0.013	N	0.554	neutral	N	0.467984515	None	None	N
R/M	0.3138	likely_benign	0.3513	ambiguous	-1.548	Destabilizing	0.949	D	0.692	prob.neutral	None	None	None	None	N
R/N	0.856	likely_pathogenic	0.8583	pathogenic	-1.687	Destabilizing	0.842	D	0.595	neutral	None	None	None	None	N
R/P	0.9931	likely_pathogenic	0.9933	pathogenic	-1.455	Destabilizing	0.986	D	0.71	prob.delet.	N	0.503627275	None	None	N
R/Q	0.1151	likely_benign	0.1198	benign	-1.505	Destabilizing	0.915	D	0.63	neutral	None	None	None	None	N
R/S	0.6846	likely_pathogenic	0.7013	pathogenic	-2.603	Highly Destabilizing	0.055	N	0.379	neutral	N	0.517094722	None	None	N
R/T	0.5207	ambiguous	0.5392	ambiguous	-2.107	Highly Destabilizing	0.525	D	0.568	neutral	None	None	None	None	N
R/V	0.5053	ambiguous	0.5493	ambiguous	-1.455	Destabilizing	0.728	D	0.671	neutral	None	None	None	None	N
R/W	0.2635	likely_benign	0.2863	benign	-0.657	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
R/Y	0.4295	ambiguous	0.4605	ambiguous	-0.623	Destabilizing	0.991	D	0.699	prob.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.