TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24134	72625;72626;72627	chr2:178573732;178573731;178573730	chr2:179438459;179438458;179438457
N2AB	22493	67702;67703;67704	chr2:178573732;178573731;178573730	chr2:179438459;179438458;179438457
N2A	21566	64921;64922;64923	chr2:178573732;178573731;178573730	chr2:179438459;179438458;179438457
N2B	15069	45430;45431;45432	chr2:178573732;178573731;178573730	chr2:179438459;179438458;179438457
Novex-1	15194	45805;45806;45807	chr2:178573732;178573731;178573730	chr2:179438459;179438458;179438457
Novex-2	15261	46006;46007;46008	chr2:178573732;178573731;178573730	chr2:179438459;179438458;179438457
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: Fn3-63
• Domain position: 13
• Structural Position: 14
• Q(SASA): 0.204
• 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	None	None	0.027	N	0.369	0.219	0.266385636622	gnomAD-4.0.0	1.7459E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.68481E-05	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	0.1567	likely_benign	0.1512	benign	-0.472	Destabilizing	0.027	N	0.369	neutral	N	0.460588078	None	None	N
E/C	0.8087	likely_pathogenic	0.8226	pathogenic	-0.197	Destabilizing	0.935	D	0.465	neutral	None	None	None	None	N
E/D	0.0655	likely_benign	0.0697	benign	-0.53	Destabilizing	None	N	0.056	neutral	N	0.370371506	None	None	N
E/F	0.8149	likely_pathogenic	0.8257	pathogenic	-0.187	Destabilizing	0.791	D	0.496	neutral	None	None	None	None	N
E/G	0.1329	likely_benign	0.1301	benign	-0.724	Destabilizing	None	N	0.15	neutral	N	0.407236383	None	None	N
E/H	0.4931	ambiguous	0.4894	ambiguous	-0.1	Destabilizing	0.555	D	0.383	neutral	None	None	None	None	N
E/I	0.5789	likely_pathogenic	0.5922	pathogenic	0.175	Stabilizing	0.555	D	0.511	neutral	None	None	None	None	N
E/K	0.2773	likely_benign	0.2752	benign	0.045	Stabilizing	0.117	N	0.285	neutral	N	0.463148381	None	None	N
E/L	0.5147	ambiguous	0.521	ambiguous	0.175	Stabilizing	0.149	N	0.495	neutral	None	None	None	None	N
E/M	0.5733	likely_pathogenic	0.5882	pathogenic	0.285	Stabilizing	0.935	D	0.435	neutral	None	None	None	None	N
E/N	0.1821	likely_benign	0.1873	benign	-0.333	Destabilizing	0.081	N	0.261	neutral	None	None	None	None	N
E/P	0.8075	likely_pathogenic	0.7959	pathogenic	-0.02	Destabilizing	0.262	N	0.419	neutral	None	None	None	None	N
E/Q	0.2028	likely_benign	0.1959	benign	-0.267	Destabilizing	0.117	N	0.337	neutral	N	0.484697089	None	None	N
E/R	0.3876	ambiguous	0.3821	ambiguous	0.31	Stabilizing	0.38	N	0.365	neutral	None	None	None	None	N
E/S	0.1642	likely_benign	0.1618	benign	-0.519	Destabilizing	0.035	N	0.272	neutral	None	None	None	None	N
E/T	0.2631	likely_benign	0.2641	benign	-0.317	Destabilizing	0.149	N	0.382	neutral	None	None	None	None	N
E/V	0.3596	ambiguous	0.3719	ambiguous	-0.02	Destabilizing	0.211	N	0.455	neutral	N	0.474730812	None	None	N
E/W	0.9125	likely_pathogenic	0.9182	pathogenic	0.002	Stabilizing	0.935	D	0.502	neutral	None	None	None	None	N
E/Y	0.6313	likely_pathogenic	0.651	pathogenic	0.056	Stabilizing	0.791	D	0.469	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.