TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5852	17779;17780;17781	chr2:178731111;178731110;178731109	chr2:179595838;179595837;179595836
N2AB	5535	16828;16829;16830	chr2:178731111;178731110;178731109	chr2:179595838;179595837;179595836
N2A	4608	14047;14048;14049	chr2:178731111;178731110;178731109	chr2:179595838;179595837;179595836
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-42
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1624
• 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
I/S	None	None	0.998	N	0.616	0.449	0.886848395655	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
I/V	None	None	0.689	N	0.327	0.149	0.531629458225	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
I/A	0.7599	likely_pathogenic	0.7138	pathogenic	-1.848	Destabilizing	0.965	D	0.482	neutral	None	None	None	None	N
I/C	0.8918	likely_pathogenic	0.8669	pathogenic	-1.349	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
I/D	0.9573	likely_pathogenic	0.9466	pathogenic	-1.001	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
I/E	0.9204	likely_pathogenic	0.8998	pathogenic	-0.945	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
I/F	0.4024	ambiguous	0.3158	benign	-1.226	Destabilizing	0.989	D	0.541	neutral	N	0.500504409	None	None	N
I/G	0.9212	likely_pathogenic	0.9009	pathogenic	-2.228	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
I/H	0.8873	likely_pathogenic	0.85	pathogenic	-1.435	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
I/K	0.7422	likely_pathogenic	0.668	pathogenic	-1.175	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
I/L	0.1293	likely_benign	0.1193	benign	-0.851	Destabilizing	0.011	N	0.121	neutral	N	0.419712609	None	None	N
I/M	0.1221	likely_benign	0.1118	benign	-0.799	Destabilizing	0.989	D	0.572	neutral	N	0.504544791	None	None	N
I/N	0.624	likely_pathogenic	0.5755	pathogenic	-1.071	Destabilizing	0.998	D	0.737	prob.delet.	D	0.534520982	None	None	N
I/P	0.8442	likely_pathogenic	0.8157	pathogenic	-1.153	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
I/Q	0.8328	likely_pathogenic	0.7864	pathogenic	-1.172	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
I/R	0.7146	likely_pathogenic	0.6342	pathogenic	-0.711	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
I/S	0.8059	likely_pathogenic	0.759	pathogenic	-1.823	Destabilizing	0.998	D	0.616	neutral	N	0.504544791	None	None	N
I/T	0.7307	likely_pathogenic	0.6744	pathogenic	-1.634	Destabilizing	0.98	D	0.576	neutral	N	0.504544791	None	None	N
I/V	0.1526	likely_benign	0.1397	benign	-1.153	Destabilizing	0.689	D	0.327	neutral	N	0.483110726	None	None	N
I/W	0.9228	likely_pathogenic	0.8939	pathogenic	-1.292	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
I/Y	0.761	likely_pathogenic	0.695	pathogenic	-1.054	Destabilizing	0.999	D	0.657	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.