TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32982	99169;99170;99171	chr2:178538991;178538990;178538989	chr2:179403718;179403717;179403716
N2AB	31341	94246;94247;94248	chr2:178538991;178538990;178538989	chr2:179403718;179403717;179403716
N2A	30414	91465;91466;91467	chr2:178538991;178538990;178538989	chr2:179403718;179403717;179403716
N2B	23917	71974;71975;71976	chr2:178538991;178538990;178538989	chr2:179403718;179403717;179403716
Novex-1	24042	72349;72350;72351	chr2:178538991;178538990;178538989	chr2:179403718;179403717;179403716
Novex-2	24109	72550;72551;72552	chr2:178538991;178538990;178538989	chr2:179403718;179403717;179403716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-128
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.7862
• 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/Q	None	None	1.0	N	0.687	0.297	0.317958651998	gnomAD-4.0.0	1.59312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-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	0.2804	likely_benign	0.2612	benign	-0.433	Destabilizing	0.999	D	0.677	prob.neutral	N	0.520308386	None	None	N
E/C	0.9434	likely_pathogenic	0.9332	pathogenic	None	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/D	0.1142	likely_benign	0.134	benign	-0.315	Destabilizing	0.999	D	0.553	neutral	N	0.44558134	None	None	N
E/F	0.9252	likely_pathogenic	0.9112	pathogenic	-0.336	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
E/G	0.2728	likely_benign	0.2462	benign	-0.616	Destabilizing	1.0	D	0.67	neutral	N	0.476128498	None	None	N
E/H	0.7153	likely_pathogenic	0.7048	pathogenic	-0.088	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
E/I	0.6827	likely_pathogenic	0.6583	pathogenic	0.011	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/K	0.2521	likely_benign	0.2149	benign	0.363	Stabilizing	0.999	D	0.664	neutral	N	0.514825208	None	None	N
E/L	0.6745	likely_pathogenic	0.6563	pathogenic	0.011	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/M	0.7466	likely_pathogenic	0.7166	pathogenic	0.162	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
E/N	0.345	ambiguous	0.3412	ambiguous	0.026	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/P	0.5591	ambiguous	0.5781	pathogenic	-0.118	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/Q	0.2541	likely_benign	0.2389	benign	0.062	Stabilizing	1.0	D	0.687	prob.neutral	N	0.511323543	None	None	N
E/R	0.4516	ambiguous	0.4124	ambiguous	0.533	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/S	0.3123	likely_benign	0.2998	benign	-0.118	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
E/T	0.4232	ambiguous	0.4032	ambiguous	0.037	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/V	0.4548	ambiguous	0.4264	ambiguous	-0.118	Destabilizing	1.0	D	0.719	prob.delet.	N	0.472889722	None	None	N
E/W	0.9749	likely_pathogenic	0.9712	pathogenic	-0.18	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Y	0.8525	likely_pathogenic	0.8389	pathogenic	-0.092	Destabilizing	1.0	D	0.697	prob.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.