TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31291	94096;94097;94098	chr2:178547755;178547754;178547753	chr2:179412482;179412481;179412480
N2AB	29650	89173;89174;89175	chr2:178547755;178547754;178547753	chr2:179412482;179412481;179412480
N2A	28723	86392;86393;86394	chr2:178547755;178547754;178547753	chr2:179412482;179412481;179412480
N2B	22226	66901;66902;66903	chr2:178547755;178547754;178547753	chr2:179412482;179412481;179412480
Novex-1	22351	67276;67277;67278	chr2:178547755;178547754;178547753	chr2:179412482;179412481;179412480
Novex-2	22418	67477;67478;67479	chr2:178547755;178547754;178547753	chr2:179412482;179412481;179412480
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-151
• Domain position: 74
• Structural Position: 159
• Q(SASA): 0.4435
• 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/G	rs1471852535	-1.149	1.0	N	0.758	0.533	0.637385919607	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/K	None	None	0.999	N	0.703	0.397	0.484109215787	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2654	likely_benign	0.3012	benign	-0.732	Destabilizing	0.999	D	0.727	prob.delet.	N	0.514223067	None	None	N
E/C	0.8893	likely_pathogenic	0.9096	pathogenic	-0.096	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/D	0.3223	likely_benign	0.3957	ambiguous	-0.697	Destabilizing	0.999	D	0.535	neutral	N	0.503698587	None	None	N
E/F	0.9139	likely_pathogenic	0.934	pathogenic	-0.66	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/G	0.3293	likely_benign	0.3807	ambiguous	-0.977	Destabilizing	1.0	D	0.758	deleterious	N	0.489317315	None	None	N
E/H	0.6283	likely_pathogenic	0.6797	pathogenic	-0.788	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/I	0.6314	likely_pathogenic	0.6672	pathogenic	-0.099	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.3271	likely_benign	0.3417	ambiguous	0.01	Stabilizing	0.999	D	0.703	prob.neutral	N	0.488593904	None	None	N
E/L	0.6741	likely_pathogenic	0.7155	pathogenic	-0.099	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/M	0.6705	likely_pathogenic	0.7024	pathogenic	0.296	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/N	0.5074	ambiguous	0.5861	pathogenic	-0.312	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/P	0.9834	likely_pathogenic	0.9878	pathogenic	-0.289	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Q	0.1616	likely_benign	0.1671	benign	-0.282	Destabilizing	1.0	D	0.704	prob.neutral	D	0.528133727	None	None	N
E/R	0.4338	ambiguous	0.4523	ambiguous	0.103	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/S	0.3143	likely_benign	0.3608	ambiguous	-0.509	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/T	0.3294	likely_benign	0.3784	ambiguous	-0.309	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/V	0.3881	ambiguous	0.4245	ambiguous	-0.289	Destabilizing	1.0	D	0.811	deleterious	N	0.516628654	None	None	N
E/W	0.9527	likely_pathogenic	0.9616	pathogenic	-0.485	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Y	0.8447	likely_pathogenic	0.8711	pathogenic	-0.411	Destabilizing	1.0	D	0.798	deleterious	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.