TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7724	23395;23396;23397	chr2:178720592;178720591;178720590	chr2:179585319;179585318;179585317
N2AB	7407	22444;22445;22446	chr2:178720592;178720591;178720590	chr2:179585319;179585318;179585317
N2A	6480	19663;19664;19665	chr2:178720592;178720591;178720590	chr2:179585319;179585318;179585317
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-62
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.7097
• 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
E/A	rs750019682	-0.688	0.755	D	0.522	0.349	0.39843156188	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/A	rs750019682	-0.688	0.755	D	0.522	0.349	0.39843156188	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85997E-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
E/A	0.1905	likely_benign	0.1989	benign	-0.507	Destabilizing	0.755	D	0.522	neutral	D	0.529672522	None	None	N
E/C	0.8853	likely_pathogenic	0.8909	pathogenic	-0.251	Destabilizing	0.997	D	0.627	neutral	None	None	None	None	N
E/D	0.2879	likely_benign	0.2703	benign	-1.112	Destabilizing	0.284	N	0.517	neutral	D	0.523111909	None	None	N
E/F	0.8074	likely_pathogenic	0.8072	pathogenic	-0.687	Destabilizing	0.964	D	0.622	neutral	None	None	None	None	N
E/G	0.2678	likely_benign	0.272	benign	-0.817	Destabilizing	0.954	D	0.591	neutral	N	0.492102019	None	None	N
E/H	0.4431	ambiguous	0.4624	ambiguous	-1.076	Destabilizing	0.975	D	0.564	neutral	None	None	None	None	N
E/I	0.3874	ambiguous	0.3855	ambiguous	0.31	Stabilizing	0.861	D	0.587	neutral	None	None	None	None	N
E/K	0.1162	likely_benign	0.122	benign	-0.429	Destabilizing	0.74	D	0.537	neutral	N	0.466063761	None	None	N
E/L	0.4865	ambiguous	0.501	ambiguous	0.31	Stabilizing	0.011	N	0.382	neutral	None	None	None	None	N
E/M	0.4751	ambiguous	0.4748	ambiguous	0.775	Stabilizing	0.689	D	0.615	neutral	None	None	None	None	N
E/N	0.3235	likely_benign	0.32	benign	-0.67	Destabilizing	0.921	D	0.566	neutral	None	None	None	None	N
E/P	0.9604	likely_pathogenic	0.9576	pathogenic	0.06	Stabilizing	0.919	D	0.622	neutral	None	None	None	None	N
E/Q	0.1029	likely_benign	0.1112	benign	-0.583	Destabilizing	0.269	N	0.307	neutral	N	0.492885003	None	None	N
E/R	0.2211	likely_benign	0.2417	benign	-0.453	Destabilizing	0.052	N	0.319	neutral	None	None	None	None	N
E/S	0.2413	likely_benign	0.2472	benign	-1.003	Destabilizing	0.803	D	0.519	neutral	None	None	None	None	N
E/T	0.2263	likely_benign	0.2335	benign	-0.745	Destabilizing	0.919	D	0.576	neutral	None	None	None	None	N
E/V	0.2463	likely_benign	0.2451	benign	0.06	Stabilizing	0.487	N	0.567	neutral	D	0.527480366	None	None	N
E/W	0.9474	likely_pathogenic	0.9464	pathogenic	-0.744	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
E/Y	0.7448	likely_pathogenic	0.7427	pathogenic	-0.489	Destabilizing	0.998	D	0.619	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.