TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7126	21601;21602;21603	chr2:178723883;178723882;178723881	chr2:179588610;179588609;179588608
N2AB	6809	20650;20651;20652	chr2:178723883;178723882;178723881	chr2:179588610;179588609;179588608
N2A	5882	17869;17870;17871	chr2:178723883;178723882;178723881	chr2:179588610;179588609;179588608
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-55
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.5982
• 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
E/A	rs761736630	-0.535	0.98	N	0.565	0.499	0.544128928594	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	0	0	None	0	2.05044E-04	None	0	None	0	0	0
E/A	rs761736630	-0.535	0.98	N	0.565	0.499	0.544128928594	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92753E-04	None	0	0	0	0	0
E/A	rs761736630	-0.535	0.98	N	0.565	0.499	0.544128928594	gnomAD-4.0.0	3.10105E-06	None	None	None	None	I	None	0	0	None	0	8.91981E-05	None	0	0	8.4827E-07	0	0
E/D	rs786205315	None	0.953	N	0.493	0.493	0.271763555656	gnomAD-4.0.0	6.84861E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00233E-07	0	0
E/K	None	None	0.4	N	0.209	0.376	0.347659731818	gnomAD-4.0.0	6.84791E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00114E-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
E/A	0.1662	likely_benign	0.1598	benign	-0.911	Destabilizing	0.98	D	0.565	neutral	N	0.498902875	None	None	I
E/C	0.9206	likely_pathogenic	0.8995	pathogenic	-0.396	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/D	0.2113	likely_benign	0.1954	benign	-0.84	Destabilizing	0.953	D	0.493	neutral	N	0.495459835	None	None	I
E/F	0.7951	likely_pathogenic	0.7502	pathogenic	-0.387	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
E/G	0.2493	likely_benign	0.238	benign	-1.228	Destabilizing	0.99	D	0.594	neutral	D	0.532922566	None	None	I
E/H	0.5208	ambiguous	0.4564	ambiguous	-0.456	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	I
E/I	0.4464	ambiguous	0.3906	ambiguous	-0.058	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
E/K	0.1575	likely_benign	0.1395	benign	-0.303	Destabilizing	0.4	N	0.209	neutral	N	0.501661125	None	None	I
E/L	0.575	likely_pathogenic	0.517	ambiguous	-0.058	Destabilizing	0.985	D	0.629	neutral	None	None	None	None	I
E/M	0.5404	ambiguous	0.4982	ambiguous	0.296	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
E/N	0.3662	ambiguous	0.3301	benign	-0.808	Destabilizing	0.993	D	0.514	neutral	None	None	None	None	I
E/P	0.9491	likely_pathogenic	0.9214	pathogenic	-0.322	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	I
E/Q	0.1599	likely_benign	0.145	benign	-0.715	Destabilizing	0.659	D	0.162	neutral	N	0.505625014	None	None	I
E/R	0.2912	likely_benign	0.2465	benign	0.009	Stabilizing	0.971	D	0.477	neutral	None	None	None	None	I
E/S	0.2099	likely_benign	0.1984	benign	-1.056	Destabilizing	0.985	D	0.513	neutral	None	None	None	None	I
E/T	0.2179	likely_benign	0.1889	benign	-0.791	Destabilizing	0.993	D	0.589	neutral	None	None	None	None	I
E/V	0.2591	likely_benign	0.227	benign	-0.322	Destabilizing	0.997	D	0.622	neutral	N	0.507576609	None	None	I
E/W	0.9372	likely_pathogenic	0.9152	pathogenic	-0.072	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
E/Y	0.6943	likely_pathogenic	0.6315	pathogenic	-0.112	Destabilizing	0.999	D	0.681	prob.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.