TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35351	106276;106277;106278	chr2:178530564;178530563;178530562	chr2:179395291;179395290;179395289
N2AB	33710	101353;101354;101355	chr2:178530564;178530563;178530562	chr2:179395291;179395290;179395289
N2A	32783	98572;98573;98574	chr2:178530564;178530563;178530562	chr2:179395291;179395290;179395289
N2B	26286	79081;79082;79083	chr2:178530564;178530563;178530562	chr2:179395291;179395290;179395289
Novex-1	26411	79456;79457;79458	chr2:178530564;178530563;178530562	chr2:179395291;179395290;179395289
Novex-2	26478	79657;79658;79659	chr2:178530564;178530563;178530562	chr2:179395291;179395290;179395289
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-165
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.4747
• 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/K	rs1688663690	None	0.811	N	0.383	0.174	0.163833314356	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
E/K	rs1688663690	None	0.811	N	0.383	0.174	0.163833314356	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.06868E-04	0
E/Q	rs1688663690	None	0.211	N	0.235	0.096	0.146414634003	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	3.16456E-03	0	0	0
E/Q	rs1688663690	None	0.211	N	0.235	0.096	0.146414634003	gnomAD-4.0.0	2.56117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	4.50248E-04	0	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	0.1193	likely_benign	0.1114	benign	-0.018	Destabilizing	0.896	D	0.382	neutral	N	0.466603534	None	None	N
E/C	0.8873	likely_pathogenic	0.8833	pathogenic	0.04	Stabilizing	0.999	D	0.6	neutral	None	None	None	None	N
E/D	0.1406	likely_benign	0.1406	benign	-0.19	Destabilizing	0.026	N	0.217	neutral	N	0.442813374	None	None	N
E/F	0.7643	likely_pathogenic	0.7581	pathogenic	-0.142	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	N
E/G	0.1522	likely_benign	0.1473	benign	-0.124	Destabilizing	0.896	D	0.395	neutral	N	0.438698771	None	None	N
E/H	0.507	ambiguous	0.5063	ambiguous	0.344	Stabilizing	0.988	D	0.282	neutral	None	None	None	None	N
E/I	0.3769	ambiguous	0.3647	ambiguous	0.2	Stabilizing	0.988	D	0.515	neutral	None	None	None	None	N
E/K	0.116	likely_benign	0.1084	benign	0.514	Stabilizing	0.811	D	0.383	neutral	N	0.449135281	None	None	N
E/L	0.4309	ambiguous	0.42	ambiguous	0.2	Stabilizing	0.976	D	0.456	neutral	None	None	None	None	N
E/M	0.5013	ambiguous	0.4909	ambiguous	0.117	Stabilizing	0.999	D	0.464	neutral	None	None	None	None	N
E/N	0.2665	likely_benign	0.2604	benign	0.372	Stabilizing	0.919	D	0.292	neutral	None	None	None	None	N
E/P	0.4345	ambiguous	0.3874	ambiguous	0.145	Stabilizing	0.988	D	0.33	neutral	None	None	None	None	N
E/Q	0.1653	likely_benign	0.1602	benign	0.371	Stabilizing	0.211	N	0.235	neutral	N	0.495427718	None	None	N
E/R	0.2457	likely_benign	0.2347	benign	0.642	Stabilizing	0.076	N	0.255	neutral	None	None	None	None	N
E/S	0.1866	likely_benign	0.1782	benign	0.216	Stabilizing	0.919	D	0.317	neutral	None	None	None	None	N
E/T	0.2352	likely_benign	0.2222	benign	0.308	Stabilizing	0.919	D	0.322	neutral	None	None	None	None	N
E/V	0.2223	likely_benign	0.2178	benign	0.145	Stabilizing	0.984	D	0.399	neutral	N	0.473820295	None	None	N
E/W	0.9127	likely_pathogenic	0.9069	pathogenic	-0.122	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
E/Y	0.6447	likely_pathogenic	0.6359	pathogenic	0.076	Stabilizing	0.996	D	0.444	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.