TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28034	84325;84326;84327	chr2:178562032;178562031;178562030	chr2:179426759;179426758;179426757
N2AB	26393	79402;79403;79404	chr2:178562032;178562031;178562030	chr2:179426759;179426758;179426757
N2A	25466	76621;76622;76623	chr2:178562032;178562031;178562030	chr2:179426759;179426758;179426757
N2B	18969	57130;57131;57132	chr2:178562032;178562031;178562030	chr2:179426759;179426758;179426757
Novex-1	19094	57505;57506;57507	chr2:178562032;178562031;178562030	chr2:179426759;179426758;179426757
Novex-2	19161	57706;57707;57708	chr2:178562032;178562031;178562030	chr2:179426759;179426758;179426757
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-142
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.3905
• 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	rs1243085385	None	0.998	N	0.446	0.343	0.240491677333	gnomAD-4.0.0	6.84403E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99562E-07	0	0
E/V	None	None	0.733	N	0.49	0.209	0.324161360171	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.1972	likely_benign	0.2222	benign	-0.873	Destabilizing	0.989	D	0.515	neutral	N	0.476159672	None	None	N
E/C	0.7911	likely_pathogenic	0.8208	pathogenic	-0.711	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/D	0.1699	likely_benign	0.1819	benign	-1.544	Destabilizing	0.998	D	0.379	neutral	N	0.499479248	None	None	N
E/F	0.6692	likely_pathogenic	0.6853	pathogenic	-1.035	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
E/G	0.2337	likely_benign	0.2736	benign	-1.22	Destabilizing	0.999	D	0.703	prob.neutral	N	0.502980914	None	None	N
E/H	0.4051	ambiguous	0.4304	ambiguous	-1.274	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
E/I	0.3298	likely_benign	0.3264	benign	0.074	Stabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
E/K	0.203	likely_benign	0.2347	benign	-0.9	Destabilizing	0.998	D	0.446	neutral	N	0.501498046	None	None	N
E/L	0.3507	ambiguous	0.3779	ambiguous	0.074	Stabilizing	0.983	D	0.678	prob.neutral	None	None	None	None	N
E/M	0.397	ambiguous	0.4143	ambiguous	0.544	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/N	0.3105	likely_benign	0.3187	benign	-1.152	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/P	0.9522	likely_pathogenic	0.9605	pathogenic	-0.221	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.1378	likely_benign	0.1475	benign	-0.985	Destabilizing	0.999	D	0.609	neutral	N	0.477333108	None	None	N
E/R	0.3148	likely_benign	0.3723	ambiguous	-0.908	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/S	0.1871	likely_benign	0.2034	benign	-1.639	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	N
E/T	0.1796	likely_benign	0.1866	benign	-1.319	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
E/V	0.21	likely_benign	0.2127	benign	-0.221	Destabilizing	0.733	D	0.49	neutral	N	0.479506621	None	None	N
E/W	0.8744	likely_pathogenic	0.897	pathogenic	-1.161	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.5632	ambiguous	0.5778	pathogenic	-0.839	Destabilizing	1.0	D	0.813	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.